Tropomyosin - Revision history

Michal Harel at 11:38, 23 January 2024

Michal Harel — Tue, 23 Jan 2024 11:38:39 GMT

←Older revision		Revision as of 11:38, 23 January 2024
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	[[Tropomyosin 3D structures]]		[[Tropomyosin 3D structures]]
-
-	</StructureSection>
-	== 3D structures of Tropomyosin ==
-
-	Updated on {{REVISIONDAY2}}-{{MONTHNAME\|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
-	{{#tree:id=OrganizedByTopic\|openlevels=0\|
-
-	*Tropomyosin
-
-	**[[5kht]] – TPM α-1 N terminal - human<br />
-	**[[6otn]] - hTPM α-3 N-terminal <br />
-	**[[1c1g]] – pTPM – pig<br />
-	**[[6klq]], [[6klp]] - mTPM – mouse - Cryo EM<br />
-	**[[1mv4]] - rTPM α-1 C-terminal - rat<br />
-	**[[2b9c]] – rTPM mid region <br />
-	**[[3azd]] – rTPM N terminal<br />
-	**[[3mtu]], [[3mud]] – cTPM α-1 – chicken<br />
-	**[[1ic2]] - cTPM α-1 (mutant)<br />
-	**[[3u1a]], [[3u1c]] – cTPM α-1 N terminal<br />
-	**[[3u59]] – cTPM β N terminal<br />
-	**[[7bjg]], [[7bjn]] – DmTPM 270-334 – ''Drosophila melanogaster''<br />
-	**[[2tma]] – TPM - model<br />
-
-	*Tropomyosin complexes
-
-	**[[6kn8]], [[6kn7]] - hTPM α-1 + troponin + actin – Cryo EM<br />
-	**[[6x5z]] - hTPM α-1 + myosin-7 + cActin – Cryo EM<br />
-	**[[5jlh]] - hTPM α-3 + myosin-14 + actin – Cryo EM<br />
-	**[[6g2t]], [[6cxj]], [[6cxi]] - hTPM + myosin-binding protein + actin – Cryo EM<br />
-	**[[7jh7]] - pTPM + myosin-7 + actin – Cryo EM<br />
-	**[[7ko4]], [[7ko5]], [[7ko7]], [[7kon]], [[7kor]] - pTPM α-1 + troponin + actin – Cryo EM<br />
-	**[[5nog]], [[5noj]], [[5nol]] - pTPM α-1 + actin – Cryo EM<br />
-	**[[2efr]], [[2efs]], [[2d3e]] - raTPM α-1 C-terminal+GNC4 leucine zipper – rabbit<br />
-	**[[4a7f]], [[4a7h]], [[4a7l]] - raTPM α-1 + myosin IE heavy chain + actin – Cryo EM<br />
-	**[[3j4k]] - raTPM + actin – Cryo EM<br />
-	**[[7nep]] - mTPM α-1 + myosin-4 + myosin light chain + actin – Cryo EM<br />
-	**[[7qin]] - mTPM α-1 in actomyosin complex – Cryo EM<br />
-	**[[3j8a]], [[5jlf]] - mTPM + actin - Cryo EM<br />
-	**[[2g9j]] - rTPM α-1 TM9A+GNC4 <br />
-	**[[2w49]], [[2w4u]] – cTnnC+cTnnT+cTnnI+cTPM α-1 + cActin<br />
-	**[[7bjs]] – DmTPM 252-334 + kinesin heavy chain<br />
-	**[[2z5h]] – yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper+TnnT – yeast<br />
-	**[[2z5i]] - yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper<br />
-	**[[1kql]] - yTPM α-1 C-terminal+GNC4 leucine zipper <br />
-	}}

	==References==		==References==
	<references />		<references />
-		+	</StructureSection>
	[[Category: Topic Page]]		[[Category: Topic Page]]

Michal Harel at 09:43, 18 May 2022

Michal Harel — Wed, 18 May 2022 09:43:43 GMT

←Older revision		Revision as of 09:43, 18 May 2022
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	**[[6g2t]], [[6cxj]], [[6cxi]] - hTPM + myosin-binding protein + actin – Cryo EM<br />		**[[6g2t]], [[6cxj]], [[6cxi]] - hTPM + myosin-binding protein + actin – Cryo EM<br />
	**[[7jh7]] - pTPM + myosin-7 + actin – Cryo EM<br />		**[[7jh7]] - pTPM + myosin-7 + actin – Cryo EM<br />
-	**[[7ko4]], [[~~7kor5~~], [[7ko7]], [[7kon]], [[7kor]] - pTPM α-1 + troponin + actin – Cryo EM<br />	+	**[[7ko4]], [[7ko5]], [[7ko7]], [[7kon]], [[7kor]] - pTPM α-1 + troponin + actin – Cryo EM<br />
	**[[5nog]], [[5noj]], [[5nol]] - pTPM α-1 + actin – Cryo EM<br />		**[[5nog]], [[5noj]], [[5nol]] - pTPM α-1 + actin – Cryo EM<br />
	**[[2efr]], [[2efs]], [[2d3e]] - raTPM α-1 C-terminal+GNC4 leucine zipper – rabbit<br />		**[[2efr]], [[2efs]], [[2d3e]] - raTPM α-1 C-terminal+GNC4 leucine zipper – rabbit<br />

Michal Harel at 09:42, 18 May 2022

Michal Harel — Wed, 18 May 2022 09:42:35 GMT

←Older revision		Revision as of 09:42, 18 May 2022
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	<StructureSection load='' size='350' side='right' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2' caption='Pig tropomyosin (PDB code [[1c1g]])'>		<StructureSection load='' size='350' side='right' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2' caption='Pig tropomyosin (PDB code [[1c1g]])'>
	[[Image:B Lehman1.jpg \| thumb \| 300 x 430px \| left \| alt text \| '''Tropomyosin''' (seen in yellow and red) wrapped around actin filaments, which are EM reconstructions with G-actin ribbion structures filling in the EM structure. (Picture generated from William Lehman's [http://www.bumc.bu.edu/phys-biophys/research/filhel/ Website]) ]]		[[Image:B Lehman1.jpg \| thumb \| 300 x 430px \| left \| alt text \| '''Tropomyosin''' (seen in yellow and red) wrapped around actin filaments, which are EM reconstructions with G-actin ribbion structures filling in the EM structure. (Picture generated from William Lehman's [http://www.bumc.bu.edu/phys-biophys/research/filhel/ Website]) ]]
		+	__TOC__
	==Function==		==Function==
	'''[[Tropomyosin]] (TM)''' is an [[actin]] binding protein, which consists of a coiled-coil dimer (see left) and forms a polymer along the length of actin by a head-to-tail overlap along the major grove of actin (see down & left)<ref name="Gunning">Tropomyosins. I. Gunning, Peter, 1950- II. Series.[DNLM: 1. Tropomyosin. W1 AD559 v.644 2008 / WE 500 T856 2008]</ref>. See [[Coiled coil]]. The head-to-tail overlap allows flexibility between the tropomyosin dimers so it will lay unstrained along the filament<ref name="Gunning"/>. Each tropomyosin molecule spans seven actin monomers within a filament and lays N- to C- terminally from actin's pointed to barbed end<ref name="Frye">PMID:20465283</ref>. The 284 amino acid helix has a length of 420 Angstroms and has a molecular weight around 65-70 kilodaltons (vertebrate tropomyosin)<ref name="Gunning"/><ref name="Whitby">PMID:10651038</ref>. A few of tropomyosin's characteristics as an actin binding protein includes regulation, stabilization and recruitment.		'''[[Tropomyosin]] (TM)''' is an [[actin]] binding protein, which consists of a coiled-coil dimer (see left) and forms a polymer along the length of actin by a head-to-tail overlap along the major grove of actin (see down & left)<ref name="Gunning">Tropomyosins. I. Gunning, Peter, 1950- II. Series.[DNLM: 1. Tropomyosin. W1 AD559 v.644 2008 / WE 500 T856 2008]</ref>. See [[Coiled coil]]. The head-to-tail overlap allows flexibility between the tropomyosin dimers so it will lay unstrained along the filament<ref name="Gunning"/>. Each tropomyosin molecule spans seven actin monomers within a filament and lays N- to C- terminally from actin's pointed to barbed end<ref name="Frye">PMID:20465283</ref>. The 284 amino acid helix has a length of 420 Angstroms and has a molecular weight around 65-70 kilodaltons (vertebrate tropomyosin)<ref name="Gunning"/><ref name="Whitby">PMID:10651038</ref>. A few of tropomyosin's characteristics as an actin binding protein includes regulation, stabilization and recruitment.
Line 30:		Line 31:
	<br />		<br />

-	=== Post-Translational Modifications ===	+	== Post-Translational Modifications ==
	There are two types of post-translational modifications to tropomyosin: phosphorylation acetylation<ref name="Gunning"/>. Phosphorylation occurs on amino acid <scene name='41/410306/Tropomyosin_dimer_ser229/1'>Ser-229</scene><ref name="Gunning"/>. This phosphorylation is occurs as a result of oxidative stress, which is associated with actin remodeling and recruitment of additional tropomyosin into stress fibers<ref name="Gunning"/>. The acetylation occurs on the N-terminus of the N-terminal methionine, which is essential for: coiled-coil stability, overlap formation and actin binding<ref name="Frye"/><ref name="Gunning"/>.		There are two types of post-translational modifications to tropomyosin: phosphorylation acetylation<ref name="Gunning"/>. Phosphorylation occurs on amino acid <scene name='41/410306/Tropomyosin_dimer_ser229/1'>Ser-229</scene><ref name="Gunning"/>. This phosphorylation is occurs as a result of oxidative stress, which is associated with actin remodeling and recruitment of additional tropomyosin into stress fibers<ref name="Gunning"/>. The acetylation occurs on the N-terminus of the N-terminal methionine, which is essential for: coiled-coil stability, overlap formation and actin binding<ref name="Frye"/><ref name="Gunning"/>.
	=== Evolutionary Conservation ===		=== Evolutionary Conservation ===
	Tropomyosin is highly conserved actin binding protein, which is found in Eukarya from the animal kingdom to yeast, with the exception of plants<ref name="Gunning"/>. The earliest characterization of tropomyosin gene lineage was in yeast (budding and fission yeast)<ref name="Gunning"/><ref name="Drees">PMID:7844152</ref>. These genes are known as [http://en.wikipedia.org/wiki/TPM1 TPM1] and [http://en.wikipedia.org/wiki/TPM2 TPM2], respectively, and share 64.5% sequence identity<ref name="Gunning"/><ref name="Drees"/>. As we move away from unicellular organisms and into multicellular invertebrates, tropomyosin genes in nematodes slightly diverge from yeast, but have 85-90% sequence identity between their genes<ref name="Gunning"/>. Further analysis for vertebrates show there are four genes that generate over 40 known mammalian isoforms of tropomyosin, which are synthesized by exon splicing<ref name="Gunning"/>. The slight evolution change of tropomyosin has occurred as a result of the increasing need of tropomyosin to function in different systems, but tropomyosin has evolutionarily stayed well conserved because of the basic structural pressures imposed on the protein<ref name="Gunning"/>. It is interesting to note, the region with the least conservation has been in the N and C terminus. This is the result of head-tail interactions changing to accommodate different polymer confirmations along actin for different functions<ref name="Gunning"/>. (To see this evolutionary conservation, go to the top right image of the web page and click on the "show" link, which is to the right of "Evolutionary Conservation".)		Tropomyosin is highly conserved actin binding protein, which is found in Eukarya from the animal kingdom to yeast, with the exception of plants<ref name="Gunning"/>. The earliest characterization of tropomyosin gene lineage was in yeast (budding and fission yeast)<ref name="Gunning"/><ref name="Drees">PMID:7844152</ref>. These genes are known as [http://en.wikipedia.org/wiki/TPM1 TPM1] and [http://en.wikipedia.org/wiki/TPM2 TPM2], respectively, and share 64.5% sequence identity<ref name="Gunning"/><ref name="Drees"/>. As we move away from unicellular organisms and into multicellular invertebrates, tropomyosin genes in nematodes slightly diverge from yeast, but have 85-90% sequence identity between their genes<ref name="Gunning"/>. Further analysis for vertebrates show there are four genes that generate over 40 known mammalian isoforms of tropomyosin, which are synthesized by exon splicing<ref name="Gunning"/>. The slight evolution change of tropomyosin has occurred as a result of the increasing need of tropomyosin to function in different systems, but tropomyosin has evolutionarily stayed well conserved because of the basic structural pressures imposed on the protein<ref name="Gunning"/>. It is interesting to note, the region with the least conservation has been in the N and C terminus. This is the result of head-tail interactions changing to accommodate different polymer confirmations along actin for different functions<ref name="Gunning"/>. (To see this evolutionary conservation, go to the top right image of the web page and click on the "show" link, which is to the right of "Evolutionary Conservation".)
-

	== Tropomyosin's Function: Muscle and Non-Muscle Systems ==		== Tropomyosin's Function: Muscle and Non-Muscle Systems ==
		+
	Muscle tissue is comprised of many muscle fibers or cells. Those muscle fibers consist of myofibrils that contain a series of contractile units called sarcomeres. Within this unit contains thick filaments, comprised mainly of [[myosin]], and thin filaments, which contain [[actin]], tropomyosin and [[troponin]]. Tropomyosin in striated muscle systems (skeletal and cardiac) acts to inhibit the myosin cross-bridges from binding to the myosin binding site on thin filaments, this tropomyosin state is in the "Blocked" position<ref name="Lehman">PMID:19341744</ref>. When the muscle is stimulated, there is a rise in intracellular calcium stemming from a cascade of cellular processes. As the calcium is bathing the sarcomere, it will bind to the troponin complex, which is bound to both actin and tropomyosin<ref name="Tyska">PMID:11810692</ref>. The troponin will displace the tropomyosin from a "Blocked" to a "Closed" position<ref name="Lehman"/>. This transition allows the myosin head to interact weakly with the myosin binding site<ref name="Tyska"/>. The tropomyosin is displaced to its final position, "Open" state, along actin filament as myosin binds to its site<ref name="Lehman"/>. These three tropomyosin states along the filament is referred to as the three state model<ref name="Lehman"/>. As the intracellular calcium concentration falls, the troponin no longer is able to displace tropomyosin and it will transition back to the "Blocked" state<ref name="Lehman"/>.		Muscle tissue is comprised of many muscle fibers or cells. Those muscle fibers consist of myofibrils that contain a series of contractile units called sarcomeres. Within this unit contains thick filaments, comprised mainly of [[myosin]], and thin filaments, which contain [[actin]], tropomyosin and [[troponin]]. Tropomyosin in striated muscle systems (skeletal and cardiac) acts to inhibit the myosin cross-bridges from binding to the myosin binding site on thin filaments, this tropomyosin state is in the "Blocked" position<ref name="Lehman">PMID:19341744</ref>. When the muscle is stimulated, there is a rise in intracellular calcium stemming from a cascade of cellular processes. As the calcium is bathing the sarcomere, it will bind to the troponin complex, which is bound to both actin and tropomyosin<ref name="Tyska">PMID:11810692</ref>. The troponin will displace the tropomyosin from a "Blocked" to a "Closed" position<ref name="Lehman"/>. This transition allows the myosin head to interact weakly with the myosin binding site<ref name="Tyska"/>. The tropomyosin is displaced to its final position, "Open" state, along actin filament as myosin binds to its site<ref name="Lehman"/>. These three tropomyosin states along the filament is referred to as the three state model<ref name="Lehman"/>. As the intracellular calcium concentration falls, the troponin no longer is able to displace tropomyosin and it will transition back to the "Blocked" state<ref name="Lehman"/>.
	<br />		<br />
	<br />		<br />
	In non-muscle systems, as mentioned above, tropomyosin performs a wide variety of functions inside of cells. One of the specific functions tropomyosin performs within cells is recruitment of different myosin motors. Clayton ''et al'', 2010 showed actin decorated with tropomyosin increased myosin-V (cargo transporter) motility as opposed to bare actin<ref name="Clayton">PMID:20705471</ref>. It was also shown that myosin-I (cargo transporter and tension senor) lost its motility function on actin decorated with tropomyosin<ref name="Clayton"/>. Further evidence from a related paper, Stark ''et al'' 2010, shows tropomyosin increases the affinity of myosin-II to actin filaments<ref name="Stark">PMID:20110347</ref>. So actin decorated with tropomyosin appears to spatially regulate motor activity and thus cellular function.		In non-muscle systems, as mentioned above, tropomyosin performs a wide variety of functions inside of cells. One of the specific functions tropomyosin performs within cells is recruitment of different myosin motors. Clayton ''et al'', 2010 showed actin decorated with tropomyosin increased myosin-V (cargo transporter) motility as opposed to bare actin<ref name="Clayton">PMID:20705471</ref>. It was also shown that myosin-I (cargo transporter and tension senor) lost its motility function on actin decorated with tropomyosin<ref name="Clayton"/>. Further evidence from a related paper, Stark ''et al'' 2010, shows tropomyosin increases the affinity of myosin-II to actin filaments<ref name="Stark">PMID:20110347</ref>. So actin decorated with tropomyosin appears to spatially regulate motor activity and thus cellular function.
		+
		+	== 3D structures of Tropomyosin ==
		+
		+	[[Tropomyosin 3D structures]]

	</StructureSection>		</StructureSection>
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	**[[3u1a]], [[3u1c]] – cTPM α-1 N terminal<br />		**[[3u1a]], [[3u1c]] – cTPM α-1 N terminal<br />
	**[[3u59]] – cTPM β N terminal<br />		**[[3u59]] – cTPM β N terminal<br />
		+	**[[7bjg]], [[7bjn]] – DmTPM 270-334 – ''Drosophila melanogaster''<br />
	**[[2tma]] – TPM - model<br />		**[[2tma]] – TPM - model<br />

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	**[[6g2t]], [[6cxj]], [[6cxi]] - hTPM + myosin-binding protein + actin – Cryo EM<br />		**[[6g2t]], [[6cxj]], [[6cxi]] - hTPM + myosin-binding protein + actin – Cryo EM<br />
	**[[7jh7]] - pTPM + myosin-7 + actin – Cryo EM<br />		**[[7jh7]] - pTPM + myosin-7 + actin – Cryo EM<br />
		+	**[[7ko4]], [[7kor5], [[7ko7]], [[7kon]], [[7kor]] - pTPM α-1 + troponin + actin – Cryo EM<br />
	**[[5nog]], [[5noj]], [[5nol]] - pTPM α-1 + actin – Cryo EM<br />		**[[5nog]], [[5noj]], [[5nol]] - pTPM α-1 + actin – Cryo EM<br />
	**[[2efr]], [[2efs]], [[2d3e]] - raTPM α-1 C-terminal+GNC4 leucine zipper – rabbit<br />		**[[2efr]], [[2efs]], [[2d3e]] - raTPM α-1 C-terminal+GNC4 leucine zipper – rabbit<br />
	**[[4a7f]], [[4a7h]], [[4a7l]] - raTPM α-1 + myosin IE heavy chain + actin – Cryo EM<br />		**[[4a7f]], [[4a7h]], [[4a7l]] - raTPM α-1 + myosin IE heavy chain + actin – Cryo EM<br />
	**[[3j4k]] - raTPM + actin – Cryo EM<br />		**[[3j4k]] - raTPM + actin – Cryo EM<br />
		+	**[[7nep]] - mTPM α-1 + myosin-4 + myosin light chain + actin – Cryo EM<br />
		+	**[[7qin]] - mTPM α-1 in actomyosin complex – Cryo EM<br />
	**[[3j8a]], [[5jlf]] - mTPM + actin - Cryo EM<br />		**[[3j8a]], [[5jlf]] - mTPM + actin - Cryo EM<br />
	**[[2g9j]] - rTPM α-1 TM9A+GNC4 <br />		**[[2g9j]] - rTPM α-1 TM9A+GNC4 <br />
	**[[2w49]], [[2w4u]] – cTnnC+cTnnT+cTnnI+cTPM α-1 + cActin<br />		**[[2w49]], [[2w4u]] – cTnnC+cTnnT+cTnnI+cTPM α-1 + cActin<br />
		+	**[[7bjs]] – DmTPM 252-334 + kinesin heavy chain<br />
	**[[2z5h]] – yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper+TnnT – yeast<br />		**[[2z5h]] – yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper+TnnT – yeast<br />
	**[[2z5i]] - yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper<br />		**[[2z5i]] - yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper<br />

Michal Harel at 09:07, 20 December 2020

Michal Harel — Sun, 20 Dec 2020 09:07:20 GMT

Michal Harel at 10:31, 10 March 2020

Michal Harel — Tue, 10 Mar 2020 10:31:50 GMT

←Older revision		Revision as of 10:31, 10 March 2020
Line 50:		Line 50:
	*Tropomyosin		*Tropomyosin

		+	**[[5kht]] – TPM α-1 N terminal - human<br />
		+	**[[6otn]] - hTPM α-3 N-terminal <br />
		+	**[[1c1g]] – pTPM – pig<br />
		+	**[[6klq]], [[6klp]] - mTPM – mouse - Cryo EM<br />
		+	**[[1mv4]] - rTPM α-1 C-terminal - rat<br />
		+	**[[2b9c]] – rTPM mid region <br />
		+	**[[3azd]] – rTPM N terminal<br />
	**[[3mtu]], [[3mud]] – cTPM α-1 – chicken<br />		**[[3mtu]], [[3mud]] – cTPM α-1 – chicken<br />
	**[[1ic2]] - cTPM α-1 (mutant)<br />		**[[1ic2]] - cTPM α-1 (mutant)<br />
	**[[3u1a]], [[3u1c]] – cTPM α-1 N terminal<br />		**[[3u1a]], [[3u1c]] – cTPM α-1 N terminal<br />
	**[[3u59]] – cTPM β N terminal<br />		**[[3u59]] – cTPM β N terminal<br />
-	**[[1mv4]] - rTPM α-1 C-terminal - rat<br />
-	**[[2b9c]] – rTPM mid region <br />
-	**[[3azd]] – rTPM N terminal<br />
-	**[[1c1g]] – pTPM – pig<br />
	**[[2tma]] – TPM - model<br />		**[[2tma]] – TPM - model<br />
-	**[[5kht]] – TPM α-1 N terminal - human<br />

	*Tropomyosin complexes		*Tropomyosin complexes

-	**[[~~2w49~~]], [[~~2w4u~~]] ~~– cTnnC+cTnnT+cTnnI+cTPM~~ α-1 +~~cActin~~<br />	+	**[[6kn8]], [[6kn7]] - hTPM α-1 + troponin + actin – Cryo EM<br />
-	**[[~~2z5h~~]] ~~– yTPM~~ α-~~1 N~~-~~terminal~~+C-~~terminal~~+~~GNC4 leucine zipper+TnnT~~ – ~~yeast~~<br />	+	**[[5jlh]] - hTPM α-3 + myosin + actin – Cryo EM<br />
-	**[[~~2z5i~~]] - ~~yTPM~~ α-1 ~~N-terminal~~+~~C-terminal+GNC4 leucine zipper~~<br />	+	**[[6g2t]], [[6cxj]], [[6cxi]] - hTPM + myosin-binding protein + actin – Cryo EM<br />
		+	**[[5nog]], [[5noj]], [[5nol]] - pTPM α-1 + actin – Cryo EM<br />
	**[[2efr]], [[2efs]], [[2d3e]] - raTPM α-1 C-terminal+GNC4 leucine zipper – rabbit<br />		**[[2efr]], [[2efs]], [[2d3e]] - raTPM α-1 C-terminal+GNC4 leucine zipper – rabbit<br />
	**[[4a7f]], [[4a7h]], [[4a7l]] - raTPM α-1 + myosin + actin – Cryo EM<br />		**[[4a7f]], [[4a7h]], [[4a7l]] - raTPM α-1 + myosin + actin – Cryo EM<br />
	**[[3j4k]] - raTPM + actin – Cryo EM<br />		**[[3j4k]] - raTPM + actin – Cryo EM<br />
-	**[[3j8a]], [[5jlf]] - ~~TPM~~ + actin ~~– mouse~~ - Cryo EM~~<br />~~	+	**[[3j8a]], [[5jlf]] - mTPM + actin - Cryo EM<br />
-	**[[1kql]] - TPM α-1 C-terminal+GNC4 leucine zipper <br />	+
	**[[2g9j]] - rTPM α-1 TM9A+GNC4 <br />		**[[2g9j]] - rTPM α-1 TM9A+GNC4 <br />
-	**[[~~5nog~~]], [[~~5noj~~]], [[~~5nol~~]] ~~- pTPM~~ α-1 + ~~actin~~ – ~~Cryo EM~~<br />	+	**[[2w49]], [[2w4u]] – cTnnC+cTnnT+cTnnI+cTPM α-1 +cActin<br />
		+	**[[2z5h]] – yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper+TnnT – yeast<br />
		+	**[[2z5i]] - yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper<br />
		+	**[[1kql]] - yTPM α-1 C-terminal+GNC4 leucine zipper <br />
	}}		}}

Michal Harel at 11:31, 22 January 2019

Michal Harel — Tue, 22 Jan 2019 11:31:45 GMT

←Older revision		Revision as of 11:31, 22 January 2019
Line 2:		Line 2:
	[[Image:B Lehman1.jpg \| thumb \| 300 x 430px \| left \| alt text \| '''Tropomyosin''' (seen in yellow and red) wrapped around actin filaments, which are EM reconstructions with G-actin ribbion structures filling in the EM structure. (Picture generated from William Lehman's [http://www.bumc.bu.edu/phys-biophys/research/filhel/ Website]) ]]		[[Image:B Lehman1.jpg \| thumb \| 300 x 430px \| left \| alt text \| '''Tropomyosin''' (seen in yellow and red) wrapped around actin filaments, which are EM reconstructions with G-actin ribbion structures filling in the EM structure. (Picture generated from William Lehman's [http://www.bumc.bu.edu/phys-biophys/research/filhel/ Website]) ]]
	==Function==		==Function==
-	'''[[Tropomyosin]] (TM)''' is an [[actin]] binding protein, which consists of a coiled-coil dimer (see left) and forms a polymer along the length of actin by a head-to-tail overlap along the major grove of actin (see down & left)<ref name="Gunning">Tropomyosins. I. Gunning, Peter, 1950- II. Series.[DNLM: 1. Tropomyosin. W1 AD559 v.644 2008 / WE 500 T856 2008]</ref>. The head-to-tail overlap allows flexibility between the tropomyosin dimers so it will lay unstrained along the filament<ref name="Gunning"/>. Each tropomyosin molecule spans seven actin monomers within a filament and lays N- to C- terminally from actin's pointed to barbed end<ref name="Frye">PMID:20465283</ref>. The 284 amino acid helix has a length of 420 Angstroms and has a molecular weight around 65-70 kilodaltons (vertebrate tropomyosin)<ref name="Gunning"/><ref name="Whitby">PMID:10651038</ref>. A few of tropomyosin's characteristics as an actin binding protein includes regulation, stabilization and recruitment.	+	'''[[Tropomyosin]] (TM)''' is an [[actin]] binding protein, which consists of a coiled-coil dimer (see left) and forms a polymer along the length of actin by a head-to-tail overlap along the major grove of actin (see down & left)<ref name="Gunning">Tropomyosins. I. Gunning, Peter, 1950- II. Series.[DNLM: 1. Tropomyosin. W1 AD559 v.644 2008 / WE 500 T856 2008]</ref>. See [[Coiled coil]]. The head-to-tail overlap allows flexibility between the tropomyosin dimers so it will lay unstrained along the filament<ref name="Gunning"/>. Each tropomyosin molecule spans seven actin monomers within a filament and lays N- to C- terminally from actin's pointed to barbed end<ref name="Frye">PMID:20465283</ref>. The 284 amino acid helix has a length of 420 Angstroms and has a molecular weight around 65-70 kilodaltons (vertebrate tropomyosin)<ref name="Gunning"/><ref name="Whitby">PMID:10651038</ref>. A few of tropomyosin's characteristics as an actin binding protein includes regulation, stabilization and recruitment.
	<br />		<br />
	Its role in muscle mechanics has been well established as it is a major regulatory component of the contractile apparatus, but its role in non-muscle systems is becoming evermore clear. In mammals, there are at least 40 known isoforms, which are generated by alternative splicing of multiple genes<ref name="Gunning"/><ref name="Frye"/>. These isoforms in non-muscle systems contribute to actin's stability by increasing filament rigidity and protecting the filament from actin severing proteins, like [[gelsolin]] or [http://en.wikipedia.org/wiki/Cofilin cofilin]. The different isoforms also aid in recruitment of various proteins, including myosin (a family of molecular motors)<ref name="Clayton"/><ref name="Stark"/>. The reason for tropomyosin's diversity is not well known, but it is thought to exist to function at different developmental stages in some species as well as function in specific cells of higher multicellular organisms<ref name="Gunning"/>.		Its role in muscle mechanics has been well established as it is a major regulatory component of the contractile apparatus, but its role in non-muscle systems is becoming evermore clear. In mammals, there are at least 40 known isoforms, which are generated by alternative splicing of multiple genes<ref name="Gunning"/><ref name="Frye"/>. These isoforms in non-muscle systems contribute to actin's stability by increasing filament rigidity and protecting the filament from actin severing proteins, like [[gelsolin]] or [http://en.wikipedia.org/wiki/Cofilin cofilin]. The different isoforms also aid in recruitment of various proteins, including myosin (a family of molecular motors)<ref name="Clayton"/><ref name="Stark"/>. The reason for tropomyosin's diversity is not well known, but it is thought to exist to function at different developmental stages in some species as well as function in specific cells of higher multicellular organisms<ref name="Gunning"/>.

Joel L. Sussman at 04:29, 16 October 2017

Joel L. Sussman — Mon, 16 Oct 2017 04:29:50 GMT

←Older revision		Revision as of 04:29, 16 October 2017
Line 1:		Line 1:
-	<StructureSection load='~~1c1g~~' size='350' side='right' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2' caption='Pig tropomyosin (PDB code [[1c1g]])'>	+	<StructureSection load='' size='350' side='right' scene='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_dimer/2' caption='Pig tropomyosin (PDB code [[1c1g]])'>
	[[Image:B Lehman1.jpg \| thumb \| 300 x 430px \| left \| alt text \| '''Tropomyosin''' (seen in yellow and red) wrapped around actin filaments, which are EM reconstructions with G-actin ribbion structures filling in the EM structure. (Picture generated from William Lehman's [http://www.bumc.bu.edu/phys-biophys/research/filhel/ Website]) ]]		[[Image:B Lehman1.jpg \| thumb \| 300 x 430px \| left \| alt text \| '''Tropomyosin''' (seen in yellow and red) wrapped around actin filaments, which are EM reconstructions with G-actin ribbion structures filling in the EM structure. (Picture generated from William Lehman's [http://www.bumc.bu.edu/phys-biophys/research/filhel/ Website]) ]]
	==Function==		==Function==

Michal Harel at 21:24, 11 October 2017

Michal Harel — Wed, 11 Oct 2017 21:24:14 GMT

←Older revision		Revision as of 21:24, 11 October 2017
Line 50:		Line 50:
	*Tropomyosin		*Tropomyosin

-	**[[3mtu]], [[3mud]] – cTPM ~~alpha~~-1 – chicken<br />	+	**[[3mtu]], [[3mud]] – cTPM α-1 – chicken<br />
-	**[[1ic2]] - cTPM ~~alpha~~-1 (mutant)<br />	+	**[[1ic2]] - cTPM α-1 (mutant)<br />
	**[[3u1a]], [[3u1c]] – cTPM α-1 N terminal<br />		**[[3u1a]], [[3u1c]] – cTPM α-1 N terminal<br />
	**[[3u59]] – cTPM β N terminal<br />		**[[3u59]] – cTPM β N terminal<br />
-	**[[1mv4]] - rTPM ~~alpha~~-1 C-terminal - rat<br />	+	**[[1mv4]] - rTPM α-1 C-terminal - rat<br />
	**[[2b9c]] – rTPM mid region <br />		**[[2b9c]] – rTPM mid region <br />
	**[[3azd]] – rTPM N terminal<br />		**[[3azd]] – rTPM N terminal<br />
-	**[[1c1g]] – ~~TPM~~ – pig<br />	+	**[[1c1g]] – pTPM – pig<br />
	**[[2tma]] – TPM - model<br />		**[[2tma]] – TPM - model<br />
		+	**[[5kht]] – TPM α-1 N terminal - human<br />

	*Tropomyosin complexes		*Tropomyosin complexes

-	**[[2w49]], [[2w4u]] – cTnnC+cTnnT+cTnnI+cTPM ~~alpha~~-1+cActin<br />	+	**[[2w49]], [[2w4u]] – cTnnC+cTnnT+cTnnI+cTPM α-1 +cActin<br />
-	**[[2z5h]] – yTPM ~~alpha~~-1 N-terminal+C-terminal+GNC4 leucine zipper+TnnT – yeast<br />	+	**[[2z5h]] – yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper+TnnT – yeast<br />
-	**[[2z5i]] - yTPM ~~alpha~~-1 N-terminal+C-terminal+GNC4 leucine zipper<br />	+	**[[2z5i]] - yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper<br />
-	**[[2efr]], [[2efs]], [[2d3e]] - raTPM ~~alpha~~-1 C-terminal+GNC4 leucine zipper – rabbit<br />	+	**[[2efr]], [[2efs]], [[2d3e]] - raTPM α-1 C-terminal+GNC4 leucine zipper – rabbit<br />
	**[[4a7f]], [[4a7h]], [[4a7l]] - raTPM α-1 + myosin + actin – Cryo EM<br />		**[[4a7f]], [[4a7h]], [[4a7l]] - raTPM α-1 + myosin + actin – Cryo EM<br />
	**[[3j4k]] - raTPM + actin – Cryo EM<br />		**[[3j4k]] - raTPM + actin – Cryo EM<br />
-	**[[3j8a]] - TPM + actin – mouse<br />	+	**[[3j8a]], [[5jlf]] - TPM + actin – mouse - Cryo EM<br />
-	**[[1kql]] - TPM ~~alpha~~-1 C-terminal+GNC4 leucine zipper <br />	+	**[[1kql]] - TPM α-1 C-terminal+GNC4 leucine zipper <br />
-	**[[2g9j]] - rTPM ~~alpha~~-1 TM9A+GNC4 <br />	+	**[[2g9j]] - rTPM α-1 TM9A+GNC4 <br />
		+	**[[5nog]], [[5noj]], [[5nol]] - pTPM α-1 + actin – Cryo EM<br />
	}}		}}

Alexander Berchansky at 08:30, 9 July 2017

Alexander Berchansky — Sun, 09 Jul 2017 08:30:21 GMT

←Older revision		Revision as of 08:30, 9 July 2017
Line 31:		Line 31:

	=== Post-Translational Modifications ===		=== Post-Translational Modifications ===
-	There are two types of post-translational modifications to tropomyosin: phosphorylation acetylation<ref name="Gunning"/>. Phosphorylation occurs on amino acid <scene name='~~User:Gregory_Hoeprich~~/~~Sandbox_1~~/Tropomyosin_dimer_ser229/1'>Ser-229</scene><ref name="Gunning"/>. This phosphorylation is occurs as a result of oxidative stress, which is associated with actin remodeling and recruitment of additional tropomyosin into stress fibers<ref name="Gunning"/>. The acetylation occurs on the N-terminus of the N-terminal methionine, which is essential for: coiled-coil stability, overlap formation and actin binding<ref name="Frye"/><ref name="Gunning"/>.	+	There are two types of post-translational modifications to tropomyosin: phosphorylation acetylation<ref name="Gunning"/>. Phosphorylation occurs on amino acid <scene name='41/410306/Tropomyosin_dimer_ser229/1'>Ser-229</scene><ref name="Gunning"/>. This phosphorylation is occurs as a result of oxidative stress, which is associated with actin remodeling and recruitment of additional tropomyosin into stress fibers<ref name="Gunning"/>. The acetylation occurs on the N-terminus of the N-terminal methionine, which is essential for: coiled-coil stability, overlap formation and actin binding<ref name="Frye"/><ref name="Gunning"/>.
	=== Evolutionary Conservation ===		=== Evolutionary Conservation ===
	Tropomyosin is highly conserved actin binding protein, which is found in Eukarya from the animal kingdom to yeast, with the exception of plants<ref name="Gunning"/>. The earliest characterization of tropomyosin gene lineage was in yeast (budding and fission yeast)<ref name="Gunning"/><ref name="Drees">PMID:7844152</ref>. These genes are known as [http://en.wikipedia.org/wiki/TPM1 TPM1] and [http://en.wikipedia.org/wiki/TPM2 TPM2], respectively, and share 64.5% sequence identity<ref name="Gunning"/><ref name="Drees"/>. As we move away from unicellular organisms and into multicellular invertebrates, tropomyosin genes in nematodes slightly diverge from yeast, but have 85-90% sequence identity between their genes<ref name="Gunning"/>. Further analysis for vertebrates show there are four genes that generate over 40 known mammalian isoforms of tropomyosin, which are synthesized by exon splicing<ref name="Gunning"/>. The slight evolution change of tropomyosin has occurred as a result of the increasing need of tropomyosin to function in different systems, but tropomyosin has evolutionarily stayed well conserved because of the basic structural pressures imposed on the protein<ref name="Gunning"/>. It is interesting to note, the region with the least conservation has been in the N and C terminus. This is the result of head-tail interactions changing to accommodate different polymer confirmations along actin for different functions<ref name="Gunning"/>. (To see this evolutionary conservation, go to the top right image of the web page and click on the "show" link, which is to the right of "Evolutionary Conservation".)		Tropomyosin is highly conserved actin binding protein, which is found in Eukarya from the animal kingdom to yeast, with the exception of plants<ref name="Gunning"/>. The earliest characterization of tropomyosin gene lineage was in yeast (budding and fission yeast)<ref name="Gunning"/><ref name="Drees">PMID:7844152</ref>. These genes are known as [http://en.wikipedia.org/wiki/TPM1 TPM1] and [http://en.wikipedia.org/wiki/TPM2 TPM2], respectively, and share 64.5% sequence identity<ref name="Gunning"/><ref name="Drees"/>. As we move away from unicellular organisms and into multicellular invertebrates, tropomyosin genes in nematodes slightly diverge from yeast, but have 85-90% sequence identity between their genes<ref name="Gunning"/>. Further analysis for vertebrates show there are four genes that generate over 40 known mammalian isoforms of tropomyosin, which are synthesized by exon splicing<ref name="Gunning"/>. The slight evolution change of tropomyosin has occurred as a result of the increasing need of tropomyosin to function in different systems, but tropomyosin has evolutionarily stayed well conserved because of the basic structural pressures imposed on the protein<ref name="Gunning"/>. It is interesting to note, the region with the least conservation has been in the N and C terminus. This is the result of head-tail interactions changing to accommodate different polymer confirmations along actin for different functions<ref name="Gunning"/>. (To see this evolutionary conservation, go to the top right image of the web page and click on the "show" link, which is to the right of "Evolutionary Conservation".)

Alexander Berchansky at 08:26, 9 July 2017

Alexander Berchansky — Sun, 09 Jul 2017 08:26:16 GMT

←Older revision		Revision as of 08:26, 9 July 2017
Line 27:		Line 27:
	<br />		<br />
	<br />		<br />
-	Tropomyosin, as mentioned above, will form a long polymer along the length of actin in a head-to-tail overlap<ref name="Frye"/>. This <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap/2'>overlap region</scene> occurs as the amino acids from the <scene name='41/410306/Tropomyosin_overlap_c_d/1'>N-terminus</scene> of one dimer overlaps with the amino acids of the <scene name='~~User:Gregory_Hoeprich~~/~~Sandbox_1~~/Tropomyosin_overlap_a_b/3'>C-terminus</scene> of another dimer. There are several <scene name='~~User:Gregory_Hoeprich~~/~~Sandbox_1~~/Tropomyosin_overlap_a_b_e_f/1'>intermolecular contacts</scene> in the overlap region, which consist of ionic, hydrophobic and non-polar interactions<ref name="Frye"/>. (Note: many of the methionine residues interacting between the dimers are selenomethionine, which are used here to help solve the x-ray crystal structure.) Interestingly, most of the variation seen among tropomyosin isoforms is in the overlap region, which will affect polymer formation along the actin filament<ref name="Frye"/>. The actin binding sites on tropomyosin (protein-protein interactions) are currently not easily recognizable, but it is thought that a periodic repeat of seven consensus residues contribute to tropomyosin binding to actin<ref name="Gunning"/>. The seven fold repeat is a mix of charged and non-polar residues in the 2,3 and 6 positions (see helical wheel diagram above)<ref name="Gunning"/>.	+	Tropomyosin, as mentioned above, will form a long polymer along the length of actin in a head-to-tail overlap<ref name="Frye"/>. This <scene name='User:Gregory_Hoeprich/Sandbox_1/Tropomyosin_overlap/2'>overlap region</scene> occurs as the amino acids from the <scene name='41/410306/Tropomyosin_overlap_c_d/1'>N-terminus</scene> of one dimer overlaps with the amino acids of the <scene name='41/410306/Tropomyosin_overlap_a_b/1'>C-terminus</scene> of another dimer. There are several <scene name='41/410306/Tropomyosin_overlap_a_b_e_f/1'>intermolecular contacts</scene> in the overlap region, which consist of ionic, hydrophobic and non-polar interactions<ref name="Frye"/>. (Note: many of the methionine residues interacting between the dimers are selenomethionine, which are used here to help solve the x-ray crystal structure.) Interestingly, most of the variation seen among tropomyosin isoforms is in the overlap region, which will affect polymer formation along the actin filament<ref name="Frye"/>. The actin binding sites on tropomyosin (protein-protein interactions) are currently not easily recognizable, but it is thought that a periodic repeat of seven consensus residues contribute to tropomyosin binding to actin<ref name="Gunning"/>. The seven fold repeat is a mix of charged and non-polar residues in the 2,3 and 6 positions (see helical wheel diagram above)<ref name="Gunning"/>.
	<br />		<br />

←Older revision		Revision as of 09:07, 20 December 2020
Line 66:		Line 66:

	**[[6kn8]], [[6kn7]] - hTPM α-1 + troponin + actin – Cryo EM<br />		**[[6kn8]], [[6kn7]] - hTPM α-1 + troponin + actin – Cryo EM<br />
-	**[[5jlh]] - hTPM α-3 + myosin + actin – Cryo EM<br />	+	**[[6x5z]] - hTPM α-1 + myosin-7 + cActin – Cryo EM<br />
		+	**[[5jlh]] - hTPM α-3 + myosin-14 + actin – Cryo EM<br />
	**[[6g2t]], [[6cxj]], [[6cxi]] - hTPM + myosin-binding protein + actin – Cryo EM<br />		**[[6g2t]], [[6cxj]], [[6cxi]] - hTPM + myosin-binding protein + actin – Cryo EM<br />
		+	**[[7jh7]] - pTPM + myosin-7 + actin – Cryo EM<br />
	**[[5nog]], [[5noj]], [[5nol]] - pTPM α-1 + actin – Cryo EM<br />		**[[5nog]], [[5noj]], [[5nol]] - pTPM α-1 + actin – Cryo EM<br />
	**[[2efr]], [[2efs]], [[2d3e]] - raTPM α-1 C-terminal+GNC4 leucine zipper – rabbit<br />		**[[2efr]], [[2efs]], [[2d3e]] - raTPM α-1 C-terminal+GNC4 leucine zipper – rabbit<br />
-	**[[4a7f]], [[4a7h]], [[4a7l]] - raTPM α-1 + myosin + actin – Cryo EM<br />	+	**[[4a7f]], [[4a7h]], [[4a7l]] - raTPM α-1 + myosin IE heavy chain + actin – Cryo EM<br />
	**[[3j4k]] - raTPM + actin – Cryo EM<br />		**[[3j4k]] - raTPM + actin – Cryo EM<br />
	**[[3j8a]], [[5jlf]] - mTPM + actin - Cryo EM<br />		**[[3j8a]], [[5jlf]] - mTPM + actin - Cryo EM<br />
	**[[2g9j]] - rTPM α-1 TM9A+GNC4 <br />		**[[2g9j]] - rTPM α-1 TM9A+GNC4 <br />
-	**[[2w49]], [[2w4u]] – cTnnC+cTnnT+cTnnI+cTPM α-1 +cActin<br />	+	**[[2w49]], [[2w4u]] – cTnnC+cTnnT+cTnnI+cTPM α-1 + cActin<br />
	**[[2z5h]] – yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper+TnnT – yeast<br />		**[[2z5h]] – yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper+TnnT – yeast<br />
	**[[2z5i]] - yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper<br />		**[[2z5i]] - yTPM α-1 N-terminal+C-terminal+GNC4 leucine zipper<br />