Circadian Clock Protein KaiC - Revision history

Alexander Berchansky at 10:57, 2 January 2020

Alexander Berchansky — Thu, 02 Jan 2020 10:57:22 GMT

←Older revision		Revision as of 10:57, 2 January 2020
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		+	<StructureSection load='1tf7' size='350' side='right' caption='Structure of KaiC complex with ATP (PDB entry [[1tf7]])' scene=''>
	==Introduction==		==Introduction==
	[[Image:KaiCABinteraction.jpg \| thumb \| alt=text \| Interactions of KaiC with KaiA and KaiB ]]		[[Image:KaiCABinteraction.jpg \| thumb \| alt=text \| Interactions of KaiC with KaiA and KaiB ]]
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-	~~<StructureSection load='1tf7' size='500' side='left' caption='Structure of KaiC complex with ATP (PDB entry [[1tf7]])' scene=''>~~	+
	== KaiC Homohexameric Complex ==		== KaiC Homohexameric Complex ==
	[[Image:ATP-1TF7 psv v 500.png \| thumb \| alt=text \| Intramolecular interactions of ATP binding site ]]		[[Image:ATP-1TF7 psv v 500.png \| thumb \| alt=text \| Intramolecular interactions of ATP binding site ]]

Michal Harel at 10:23, 15 July 2013

Michal Harel — Mon, 15 Jul 2013 10:23:42 GMT

←Older revision		Revision as of 10:23, 15 July 2013
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-	<StructureSection load='1tf7' size='500' side='left' caption='Structure of KaiC (PDB entry [[1tf7]])' scene=''>	+	<StructureSection load='1tf7' size='500' side='left' caption='Structure of KaiC complex with ATP (PDB entry [[1tf7]])' scene=''>
	== KaiC Homohexameric Complex ==		== KaiC Homohexameric Complex ==
	[[Image:ATP-1TF7 psv v 500.png \| thumb \| alt=text \| Intramolecular interactions of ATP binding site ]]		[[Image:ATP-1TF7 psv v 500.png \| thumb \| alt=text \| Intramolecular interactions of ATP binding site ]]

Jaime Prilusky at 12:18, 14 March 2013

Jaime Prilusky — Thu, 14 Mar 2013 12:18:39 GMT

←Older revision		Revision as of 12:18, 14 March 2013
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-	<StructureSection load='~~1TF7~~' size='500' side='left' caption='Structure of KaiC (PDB entry [[1tf7]])' scene=''>	+	<StructureSection load='1tf7' size='500' side='left' caption='Structure of KaiC (PDB entry [[1tf7]])' scene=''>
	== KaiC Homohexameric Complex ==		== KaiC Homohexameric Complex ==
	[[Image:ATP-1TF7 psv v 500.png \| thumb \| alt=text \| Intramolecular interactions of ATP binding site ]]		[[Image:ATP-1TF7 psv v 500.png \| thumb \| alt=text \| Intramolecular interactions of ATP binding site ]]

Michal Harel at 12:39, 13 March 2013

Michal Harel — Wed, 13 Mar 2013 12:39:04 GMT

←Older revision		Revision as of 12:39, 13 March 2013
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	==Introduction==		==Introduction==
	[[Image:KaiCABinteraction.jpg \| thumb \| alt=text \| Interactions of KaiC with KaiA and KaiB ]]		[[Image:KaiCABinteraction.jpg \| thumb \| alt=text \| Interactions of KaiC with KaiA and KaiB ]]
-	Biological Circadian Clocks are self-sustaining oscillators that function on a rhythmic cycle 24 hours. They exhibit a very precise time constant and temperature compensation, which allows the system to run at a steady rate independent of temperature fluctuations <ref name= Johnson> PMCID: PMC2585598 </ref>. They are found in almost all organisms, the simplest of which are cyanobacteria, which have been extensively studied in order to determine the mechanism of the fine-tuned biological process of circadian rhythmicity. In most eukaryotes, a region of the brain called the superchiasmic nuclei detects light and dark cycles, then relays the message to biological clock systems that maintain rhythmicity within the body. Conversely, cyanobacteria have a fairly modest system comprised of three proteins: KaiC, KaiA, and KaiB. The system is based around the central protein KaiC which exhibits ATP binding, inter-subunit organization, a scaffold region for Kai protein complex formation, a location where critical mutations are found, and an evolutionary link to other well-known proteins <ref name= Pattanayek> PMID: 15304218 </ref>. In order to devise an explanation for the mechanism of biological oscillators, we need to characterize the structure, function, and interactions among molecular components. To study these, scientists begin with analyzing cyanobacteria such as ''Synechococcus elongatus'', since it is the smallest organism that expresses rhythmic clock properties.	+	Biological Circadian Clocks are self-sustaining oscillators that function on a rhythmic cycle 24 hours. They exhibit a very precise time constant and temperature compensation, which allows the system to run at a steady rate independent of temperature fluctuations <ref name= Johnson> PMCID: PMC2585598 </ref>. They are found in almost all organisms, the simplest of which are cyanobacteria, which have been extensively studied in order to determine the mechanism of the fine-tuned biological process of circadian rhythmicity. In most eukaryotes, a region of the brain called the superchiasmic nuclei detects light and dark cycles, then relays the message to biological clock systems that maintain rhythmicity within the body. Conversely, cyanobacteria have a fairly modest system comprised of three proteins: '''KaiC, KaiA, and KaiB'''. The system is based around the central protein KaiC which exhibits ATP binding, inter-subunit organization, a scaffold region for Kai protein complex formation, a location where critical mutations are found, and an evolutionary link to other well-known proteins <ref name= Pattanayek> PMID: 15304218 </ref>. In order to devise an explanation for the mechanism of biological oscillators, we need to characterize the structure, function, and interactions among molecular components. To study these, scientists begin with analyzing cyanobacteria such as ''Synechococcus elongatus'', since it is the smallest organism that expresses rhythmic clock properties.

	==KaiC - KaiA - KaiB System==		==KaiC - KaiA - KaiB System==
Line 7:		Line 7:


-	<StructureSection load='1TF7' size='500' side='left' caption='Structure of KaiC (PDB entry [[~~1TF7~~]])' scene=''>	+	<StructureSection load='1TF7' size='500' side='left' caption='Structure of KaiC (PDB entry [[1tf7]])' scene=''>
	== KaiC Homohexameric Complex ==		== KaiC Homohexameric Complex ==
	[[Image:ATP-1TF7 psv v 500.png \| thumb \| alt=text \| Intramolecular interactions of ATP binding site ]]		[[Image:ATP-1TF7 psv v 500.png \| thumb \| alt=text \| Intramolecular interactions of ATP binding site ]]

Ashley Beechan at 01:16, 5 December 2012

Ashley Beechan — Wed, 05 Dec 2012 01:16:35 GMT

←Older revision		Revision as of 01:16, 5 December 2012
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	A region of each hexamer that is notable regarding the phosphorylation of KaiC is the <scene name='Circadian_Clock_Protein_KaiC/P-loop-shuttle-btw-431-432-426/1'>P-Loop</scene>. This zone is recognized as site for binding and hydrolysis of ATP. Along with the T432 site, evidence shows a shuttling of phosphates between residues <scene name='Circadian_Clock_Protein_KaiC/Active_site_t432_t426_s431/1'>S431 and T426</scene> of the P-Loop.		A region of each hexamer that is notable regarding the phosphorylation of KaiC is the <scene name='Circadian_Clock_Protein_KaiC/P-loop-shuttle-btw-431-432-426/1'>P-Loop</scene>. This zone is recognized as site for binding and hydrolysis of ATP. Along with the T432 site, evidence shows a shuttling of phosphates between residues <scene name='Circadian_Clock_Protein_KaiC/Active_site_t432_t426_s431/1'>S431 and T426</scene> of the P-Loop.

-	Based on RecA structure/function similarity, a conserved glutamate <scene name='Circadian_Clock_Protein_KaiC/P-loop-431-432-426-e318/2'>E318</scene> in CI is proposed to activate water for an attack on the gamma-phosphate of ATP in order to release the phosphate to be shuttled. The <scene name='Circadian_Clock_Protein_KaiC/Active-site-of-a-b/1'>ATP binding</scene> site within the A and B monomer and its interactions are displayed in the image on the ~~left~~ which shows hydrogen bonds and interactions between molecules which hold the ATP in the pocket.	+	Based on RecA structure/function similarity, a conserved glutamate <scene name='Circadian_Clock_Protein_KaiC/P-loop-431-432-426-e318/2'>E318</scene> in CI is proposed to activate water for an attack on the gamma-phosphate of ATP in order to release the phosphate to be shuttled. The <scene name='Circadian_Clock_Protein_KaiC/Active-site-of-a-b/1'>ATP binding</scene> site within the A and B monomer and its interactions are displayed in the image on the right which shows hydrogen bonds and interactions between molecules which hold the ATP in the pocket.

	==KaiA - KaiC Interaction Site==		==KaiA - KaiC Interaction Site==

Ashley Beechan: /* Biological Importance and Evolutionary Complementarity */

Ashley Beechan — Wed, 05 Dec 2012 01:01:16 GMT

Biological Importance and Evolutionary Complementarity

←Older revision		Revision as of 01:01, 5 December 2012
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	[[Image:ATP-bind-site-cI(A-cropped).jpg \| thumb \| alt=text \| Secondary Structure of Monomers ]]		[[Image:ATP-bind-site-cI(A-cropped).jpg \| thumb \| alt=text \| Secondary Structure of Monomers ]]
	In cyanobacteria, the KaiC system is vital to survival because of it's role in global gene regulation: nearly all promoters in a cyanobacteria are under circadian control. Correlating with a circadian clock system enhances fitness of any organism in a rhythmic environment <ref name= Yao> PMCID: PMC518856 </ref>.		In cyanobacteria, the KaiC system is vital to survival because of it's role in global gene regulation: nearly all promoters in a cyanobacteria are under circadian control. Correlating with a circadian clock system enhances fitness of any organism in a rhythmic environment <ref name= Yao> PMCID: PMC518856 </ref>.
-	Structure similarity exists between KaiC and RecA and DnaB. RecA is a DNA recombinase and DnaB is a DNA helicase, so the observation that there is similarity between these molecules imply possible direct interactions with DNA. The folds of each monomer resemble those of RecA, where eight α-helices surround the twisted β-sheet made up ~~for~~ seven strands (shown in the figure on the right). The similarity indicates nucleotide binding on the carboxy side of the β-sheet <ref name= Pattanayek> PMID: 15304218</ref>. The entire hexamer also has structural similarities to proteins that do not bind DNA, such as F1-ATPase. This is consistent with the fact that KaiC has phosphotransferase activity, so it is capable of generating ATP. Yet there is more indication that KaiC acts on DNA, especially single stranded DNA, rather than pumps any small molecule through the pore. Inside the CI domain of the channel, the electrostatic potential is mostly negative, while inside the more constricted CII domain of the channel, the electrostatic potential is mostly positive.	+	Structure similarity exists between KaiC and RecA and DnaB. RecA is a DNA recombinase and DnaB is a DNA helicase, so the observation that there is similarity between these molecules imply possible direct interactions with DNA. The folds of each monomer resemble those of RecA, where eight α-helices surround the twisted β-sheet made up of seven strands (shown in the figure on the right). The similarity indicates nucleotide binding on the carboxy side of the β-sheet <ref name= Pattanayek> PMID: 15304218</ref>. The entire hexamer also has structural similarities to proteins that do not bind DNA, such as F1-ATPase. This is consistent with the fact that KaiC has phosphotransferase activity, so it is capable of generating ATP. Yet there is more indication that KaiC acts on DNA, especially single stranded DNA, rather than pumps any small molecule through the pore. Inside the CI domain of the channel, the electrostatic potential is mostly negative, while inside the more constricted CII domain of the channel, the electrostatic potential is mostly positive.
	The biological activity of KaiC is still a mystery. It may mediate changes in chromosomal torsion or interact directly with nucleic acids <ref name= Pattanayek> PMID: 15304218</ref>. It has also been shown to cause changes in DNA topology and transcription factor activity <ref name= Johnson> PMCID: PMC2585598 </ref>. Based on the amount of KaiC molecules per cell (~10,000) and its DNA interaction properties, scientists are strongly persuaded that the protein regulates global gene expression by a direct mechanism that changes DNA structure.		The biological activity of KaiC is still a mystery. It may mediate changes in chromosomal torsion or interact directly with nucleic acids <ref name= Pattanayek> PMID: 15304218</ref>. It has also been shown to cause changes in DNA topology and transcription factor activity <ref name= Johnson> PMCID: PMC2585598 </ref>. Based on the amount of KaiC molecules per cell (~10,000) and its DNA interaction properties, scientists are strongly persuaded that the protein regulates global gene expression by a direct mechanism that changes DNA structure.

-	Defining the mechanism of a biological oscillator is a powerful key to the future. Although biological clock system in bacteria differs vastly from the complex network of molecules that make up eukaryotic biological clocks, it can still be useful to the understanding of circadian rhythms in general. Knowing the mechanism of KaiC can help us eradicate or reduce the harm of certain bacteria by altering their biological rhythm and therefore decreasing their fitness. On the other hand, we can enhance the fitness of other bacteria in order to exploit them for positive changes in the atmosphere, such as bioremedial techniques. The possibilities are endless with such a vital function as circadian rhythms.	+	Defining the mechanism of a biological oscillator is a powerful key to the future. Although biological clock system in bacteria differs vastly from the complex network of molecules that make up eukaryotic biological clocks, it can still be useful to the understanding of circadian rhythms in general. Knowing the mechanism of KaiC can help us eradicate or reduce the harm of certain bacteria by altering their biological rhythm and therefore decreasing their fitness. On the other hand, we can enhance the fitness of other bacteria in order to exploit them for positive changes in the atmosphere, such as bioremedial techniques. The possibilities are endless with such a vital function as circadian rhythms.

	==References==		==References==
	{{Reflist}}		{{Reflist}}

Ashley Beechan: /* Introduction */

Ashley Beechan — Wed, 05 Dec 2012 00:54:51 GMT

Introduction

←Older revision		Revision as of 00:54, 5 December 2012
Line 1:		Line 1:
	==Introduction==		==Introduction==
	[[Image:KaiCABinteraction.jpg \| thumb \| alt=text \| Interactions of KaiC with KaiA and KaiB ]]		[[Image:KaiCABinteraction.jpg \| thumb \| alt=text \| Interactions of KaiC with KaiA and KaiB ]]
-	Biological Circadian Clocks are self-sustaining oscillators that function on a rhythmic cycle ~~of or around~~ 24 hours. They exhibit a very precise time constant and temperature compensation, which allows the system to run at a steady rate independent of temperature fluctuations <ref name= Johnson> PMCID: PMC2585598 </ref>. They are found in almost all organisms, the simplest of which are cyanobacteria, which have been extensively studied in order to determine the mechanism of the fine-tuned biological process of circadian rhythmicity. In most eukaryotes, a region of the brain called the superchiasmic nuclei detects light and dark cycles, then relays the message to biological clock systems that maintain rhythmicity within the body. Conversely, cyanobacteria have a fairly modest system comprised of three proteins: KaiC, KaiA, and KaiB. The system is based around the central protein KaiC which exhibits ATP binding, inter-subunit organization, a scaffold region for Kai protein complex formation, a location where critical mutations are found, and an evolutionary link to other well-known proteins <ref name= Pattanayek> PMID: 15304218 </ref>. In order to devise an explanation for the mechanism of biological oscillators, we need to characterize the structure, function, and interactions among molecular components. To study these, scientists begin with analyzing cyanobacteria such as ''Synechococcus elongatus'', since it is the smallest organism that expresses rhythmic clock properties.	+	Biological Circadian Clocks are self-sustaining oscillators that function on a rhythmic cycle 24 hours. They exhibit a very precise time constant and temperature compensation, which allows the system to run at a steady rate independent of temperature fluctuations <ref name= Johnson> PMCID: PMC2585598 </ref>. They are found in almost all organisms, the simplest of which are cyanobacteria, which have been extensively studied in order to determine the mechanism of the fine-tuned biological process of circadian rhythmicity. In most eukaryotes, a region of the brain called the superchiasmic nuclei detects light and dark cycles, then relays the message to biological clock systems that maintain rhythmicity within the body. Conversely, cyanobacteria have a fairly modest system comprised of three proteins: KaiC, KaiA, and KaiB. The system is based around the central protein KaiC which exhibits ATP binding, inter-subunit organization, a scaffold region for Kai protein complex formation, a location where critical mutations are found, and an evolutionary link to other well-known proteins <ref name= Pattanayek> PMID: 15304218 </ref>. In order to devise an explanation for the mechanism of biological oscillators, we need to characterize the structure, function, and interactions among molecular components. To study these, scientists begin with analyzing cyanobacteria such as ''Synechococcus elongatus'', since it is the smallest organism that expresses rhythmic clock properties.

	==KaiC - KaiA - KaiB System==		==KaiC - KaiA - KaiB System==

Ashley Beechan at 23:53, 4 December 2012

Ashley Beechan — Tue, 04 Dec 2012 23:53:45 GMT

←Older revision		Revision as of 23:53, 4 December 2012
Line 38:		Line 38:
	In cyanobacteria, the KaiC system is vital to survival because of it's role in global gene regulation: nearly all promoters in a cyanobacteria are under circadian control. Correlating with a circadian clock system enhances fitness of any organism in a rhythmic environment <ref name= Yao> PMCID: PMC518856 </ref>.		In cyanobacteria, the KaiC system is vital to survival because of it's role in global gene regulation: nearly all promoters in a cyanobacteria are under circadian control. Correlating with a circadian clock system enhances fitness of any organism in a rhythmic environment <ref name= Yao> PMCID: PMC518856 </ref>.
	Structure similarity exists between KaiC and RecA and DnaB. RecA is a DNA recombinase and DnaB is a DNA helicase, so the observation that there is similarity between these molecules imply possible direct interactions with DNA. The folds of each monomer resemble those of RecA, where eight α-helices surround the twisted β-sheet made up for seven strands (shown in the figure on the right). The similarity indicates nucleotide binding on the carboxy side of the β-sheet <ref name= Pattanayek> PMID: 15304218</ref>. The entire hexamer also has structural similarities to proteins that do not bind DNA, such as F1-ATPase. This is consistent with the fact that KaiC has phosphotransferase activity, so it is capable of generating ATP. Yet there is more indication that KaiC acts on DNA, especially single stranded DNA, rather than pumps any small molecule through the pore. Inside the CI domain of the channel, the electrostatic potential is mostly negative, while inside the more constricted CII domain of the channel, the electrostatic potential is mostly positive.		Structure similarity exists between KaiC and RecA and DnaB. RecA is a DNA recombinase and DnaB is a DNA helicase, so the observation that there is similarity between these molecules imply possible direct interactions with DNA. The folds of each monomer resemble those of RecA, where eight α-helices surround the twisted β-sheet made up for seven strands (shown in the figure on the right). The similarity indicates nucleotide binding on the carboxy side of the β-sheet <ref name= Pattanayek> PMID: 15304218</ref>. The entire hexamer also has structural similarities to proteins that do not bind DNA, such as F1-ATPase. This is consistent with the fact that KaiC has phosphotransferase activity, so it is capable of generating ATP. Yet there is more indication that KaiC acts on DNA, especially single stranded DNA, rather than pumps any small molecule through the pore. Inside the CI domain of the channel, the electrostatic potential is mostly negative, while inside the more constricted CII domain of the channel, the electrostatic potential is mostly positive.
-	The biological activity of KaiC is still a mystery. It may mediate changes in chromosomal torsion or interact directly with nucleic acids <ref name= Pattanayek> PMID: 15304218</ref>. Based on the amount of KaiC molecules per cell (~10,000) and its DNA interaction properties, scientists are strongly persuaded that the protein regulates global gene expression by a direct mechanism that changes DNA structure.	+	The biological activity of KaiC is still a mystery. It may mediate changes in chromosomal torsion or interact directly with nucleic acids <ref name= Pattanayek> PMID: 15304218</ref>. It has also been shown to cause changes in DNA topology and transcription factor activity <ref name= Johnson> PMCID: PMC2585598 </ref>. Based on the amount of KaiC molecules per cell (~10,000) and its DNA interaction properties, scientists are strongly persuaded that the protein regulates global gene expression by a direct mechanism that changes DNA structure.

-	Defining the mechanism of a biological oscillator is a powerful key to the future. On ~~a smaller note~~, we can ~~treat sleeping disorders~~	+	Defining the mechanism of a biological oscillator is a powerful key to the future. Although biological clock system in bacteria differs vastly from the complex network of molecules that make up eukaryotic biological clocks, it can still be useful to the understanding of circadian rhythms in general. Knowing the mechanism of KaiC can help us eradicate or reduce the harm of certain bacteria by altering their biological rhythm and therefore decreasing their fitness. On the other hand, we can enhance the fitness of other bacteria in order to exploit them for positive changes in the atmosphere, such as bioremedial techniques. The possibilities are endless with such a vital function as circadian rhythms.

	==References==		==References==
	{{Reflist}}		{{Reflist}}

Ashley Beechan at 23:40, 4 December 2012

Ashley Beechan — Tue, 04 Dec 2012 23:40:05 GMT

←Older revision		Revision as of 23:40, 4 December 2012
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	The phosphorylation sites on the KaiC protein are essential to the system. This is because phosphorylation status corresponds to clock speed. The protein predominantly phosphorylates on threonine and serine residues, whose specific identification is not completely resolved. Nonetheless, three potential phosphorylation sites have been identified within 10 Angstroms of the ATP binding region in the CII domain <ref name= Yao>PMCID: PMC518856</ref>. The key autophosphorylation site is <scene name='Circadian_Clock_Protein_KaiC/Active_site_thr432-w_halo/1'>T432</scene>. When this residue is mutated, there is no circadian rhythm at all. The process is believed to demonstrate a transfer of the <scene name='Circadian_Clock_Protein_KaiC/Active_site_thr432_g-ptxfr/1'>δ-phosphate</scene> of ATP from one CII subunit to the T432 site on an adjacent subunit.		The phosphorylation sites on the KaiC protein are essential to the system. This is because phosphorylation status corresponds to clock speed. The protein predominantly phosphorylates on threonine and serine residues, whose specific identification is not completely resolved. Nonetheless, three potential phosphorylation sites have been identified within 10 Angstroms of the ATP binding region in the CII domain <ref name= Yao>PMCID: PMC518856</ref>. The key autophosphorylation site is <scene name='Circadian_Clock_Protein_KaiC/Active_site_thr432-w_halo/1'>T432</scene>. When this residue is mutated, there is no circadian rhythm at all. The process is believed to demonstrate a transfer of the <scene name='Circadian_Clock_Protein_KaiC/Active_site_thr432_g-ptxfr/1'>δ-phosphate</scene> of ATP from one CII subunit to the T432 site on an adjacent subunit.

-	A region of each hexamer that is notable regarding the phosphorylation of KaiC is the P Loop. This zone is recognized as site for binding and hydrolysis of ATP. Along with the T432 site, evidence shows a shuttling of phosphates between residues <scene name='Circadian_Clock_Protein_KaiC/Active_site_t432_t426_s431/1'>S431 and T426</scene> of the ~~<scene name='Circadian_Clock_Protein_KaiC/P-loop-shuttle-btw-431-432-426/1'>~~P-Loop~~</scene>~~.	+	A region of each hexamer that is notable regarding the phosphorylation of KaiC is the <scene name='Circadian_Clock_Protein_KaiC/P-loop-shuttle-btw-431-432-426/1'>P-Loop</scene>. This zone is recognized as site for binding and hydrolysis of ATP. Along with the T432 site, evidence shows a shuttling of phosphates between residues <scene name='Circadian_Clock_Protein_KaiC/Active_site_t432_t426_s431/1'>S431 and T426</scene> of the P-Loop.

-	Based on RecA structure/function similarity, a conserved glutamate <scene name='Circadian_Clock_Protein_KaiC/P-loop-431-432-426-e318/2'>E318</scene> in CI is proposed to activate water for an attack on the gamma-phosphate of ATP in order to release the phosphate to be shuttled.	+	Based on RecA structure/function similarity, a conserved glutamate <scene name='Circadian_Clock_Protein_KaiC/P-loop-431-432-426-e318/2'>E318</scene> in CI is proposed to activate water for an attack on the gamma-phosphate of ATP in order to release the phosphate to be shuttled. The <scene name='Circadian_Clock_Protein_KaiC/Active-site-of-a-b/1'>ATP binding</scene> site within the A and B monomer and its interactions are displayed in the image on the left which shows hydrogen bonds and interactions between molecules which hold the ATP in the pocket.
-	~~(difference between ATP binding and phosphorylation residues)~~	+
-	~~(Key residues = T432, S431, T426)~~	+
-	~~(show 3D image of these sites and highlight bonds/interactions)~~	+
-	The <scene name='Circadian_Clock_Protein_KaiC/Active-site-of-a-b/1'>ATP binding</scene> site within the A and B monomer and its interactions are displayed in the image on the left which shows hydrogen bonds and ~~inteeractions~~ between molecules.	+

	==KaiA - KaiC Interaction Site==		==KaiA - KaiC Interaction Site==
Line 38:		Line 34:
	</StructureSection>		</StructureSection>

-	==Biological Importance==	+	==Biological Importance and Evolutionary Complementarity==
-	In cyanobacteria, the KaiC system is vital to survival because of it's role in global gene regulation: nearly all promoters in a cyanobacteria are under circadian control. Correlating with a circadian clock system enhances fitness of any organism in a rhythmic environment. ~~[function is important to whole life cycle] (1)~~	+	[[Image:ATP-bind-site-cI(A-cropped).jpg \| thumb \| alt=text \| Secondary Structure of Monomers ]]
-	- Structure similarity ~~with~~ RecA and DnaB. RecA is a DNA recombinase and DnaB is a DNA helicase, so the observation that there is similarity between these molecules imply possible direct interactions with DNA. The folds of each monomer resemble those of RecA, where eight α-helices surround the twisted β-sheet made up for seven strands. The similarity indicates nucleotide binding on the carboxy side of the β-sheet <ref name= Pattanayek> PMID: 15304218</ref>.	+	In cyanobacteria, the KaiC system is vital to survival because of it's role in global gene regulation: nearly all promoters in a cyanobacteria are under circadian control. Correlating with a circadian clock system enhances fitness of any organism in a rhythmic environment <ref name= Yao> PMCID: PMC518856 </ref>.
		+	Structure similarity exists between KaiC and RecA and DnaB. RecA is a DNA recombinase and DnaB is a DNA helicase, so the observation that there is similarity between these molecules imply possible direct interactions with DNA. The folds of each monomer resemble those of RecA, where eight α-helices surround the twisted β-sheet made up for seven strands (shown in the figure on the right). The similarity indicates nucleotide binding on the carboxy side of the β-sheet <ref name= Pattanayek> PMID: 15304218</ref>. The entire hexamer also has structural similarities to proteins that do not bind DNA, such as F1-ATPase. This is consistent with the fact that KaiC has phosphotransferase activity, so it is capable of generating ATP. Yet there is more indication that KaiC acts on DNA, especially single stranded DNA, rather than pumps any small molecule through the pore. Inside the CI domain of the channel, the electrostatic potential is mostly negative, while inside the more constricted CII domain of the channel, the electrostatic potential is mostly positive.
		+	The biological activity of KaiC is still a mystery. It may mediate changes in chromosomal torsion or interact directly with nucleic acids <ref name= Pattanayek> PMID: 15304218</ref>. Based on the amount of KaiC molecules per cell (~10,000) and its DNA interaction properties, scientists are strongly persuaded that the protein regulates global gene expression by a direct mechanism that changes DNA structure.
		+
		+	Defining the mechanism of a biological oscillator is a powerful key to the future. On a smaller note, we can treat sleeping disorders

	==References==		==References==
	{{Reflist}}		{{Reflist}}

Ashley Beechan at 23:05, 4 December 2012

Ashley Beechan — Tue, 04 Dec 2012 23:05:49 GMT

←Older revision		Revision as of 23:05, 4 December 2012
Line 31:		Line 31:
	It is believed that two dimers of KaiA interact with one hexamer of KaiC. This could be the reason for the two binding sites hypothesized.		It is believed that two dimers of KaiA interact with one hexamer of KaiC. This could be the reason for the two binding sites hypothesized.

-	In the KaiA binding domain of KaiC, a mutation of <scene name='Circadian_Clock_Protein_KaiC/Tyrosine-to-his-mutat/1'>Tyrosine 442</scene> to a Histidine (a hydrophobic residue to a positively charged residue) lead to a 60 hour circadian period, a rhythm over twice the normal 24 hour period. This residue is located very close to the ATP binding region, indicating the possibility that the stronger binding of KaiA protects the ATP binding site to prolong its residence in the active site.	+	In the KaiA binding domain of KaiC, a mutation of <scene name='Circadian_Clock_Protein_KaiC/Tyrosine-to-his-mutat/1'>Tyrosine 442</scene> to a Histidine (a hydrophobic residue to a positively charged residue) lead to a 60 hour circadian period, a rhythm over twice the normal 24 hour period. This residue is located very close to the ATP binding region, indicating the possibility that the stronger binding of KaiA protects the ATP binding site to prolong its residence in the active site <ref name= Pattanayek>PMID: 15304218</ref>.

-	==KaiB <-> KaiC Interaction Site==	+	==KaiB - KaiC Interaction Site==
-	~~(show 3D image of~~ KaiC ~~site for~~ KaiB ~~binding~~ and ~~highlight key residues in interaction -weak? strong? ions in~~ site~~? how does~~ it ~~stabilize dephosphorylation/destabilize phosphorylation/destabilize KaiA?)~~	+	There is very little known about the interactions between KaiC and KaiB besides that KaiB antagonizes the effects of KaiA. Some possibilities based on the structure of the molecule indicate that KaiA and B compete for the same binding site, or that KaiC changes conformation of it's C-terminal domain to open to KaiB.

	</StructureSection>		</StructureSection>