1txv - Revision history

OCA: Redirecting to 2vdl

OCA — Wed, 03 Sep 2008 08:10:34 GMT

Redirecting to 2vdl

←Older revision		Revision as of 08:10, 3 September 2008
Line 1:		Line 1:
-	~~{{Seed}}~~	+	#REDIRECT [[2vdl]] This PDB entry is obsolete and replaced by 2vdl
-	[[~~Image:1txv.png\|left\|200px~~]]	+
-		+
-	~~<!--~~	+
-	~~The line below this paragraph, containing "STRUCTURE_1txv", creates the "Structure Box" on the page.~~	+
-	~~You may change the~~ PDB ~~parameter (which sets the PDB file loaded into the applet)~~	+
-	~~or the SCENE parameter (which sets the initial scene displayed when the page~~ is ~~loaded),~~	+
-	~~or leave the SCENE parameter empty for the default display.~~	+
-	~~-->~~	+
-	~~{{STRUCTURE_1txv\| PDB=1txv \| SCENE= }}~~	+
-		+
-	~~===Structural basis for allostery in integrins~~ and ~~binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen===~~	+
-		+
-		+
-	~~<!--~~	+
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_15378069}}, adds the Publication Abstract to the page~~	+
-	~~(as it appears on PubMed at http://www.pubmed.gov), where 15378069 is the PubMed ID number.~~	+
-	~~-->~~	+
-	~~{{ABSTRACT_PUBMED_15378069}}~~	+
-		+
-	~~==About this Structure==~~	+
-	1TXV is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TXV OCA].	+
-		+
-	~~==Reference==~~	+
-	Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics., Xiao T, Takagi J, Coller BS, Wang JH, Springer TA, Nature. 2004 Nov 4;432(7013):59-67. Epub 2004 Sep 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15378069 15378069]	+
-	~~[[Category: Homo sapiens]]~~	+
-	~~[[Category: Mus musculus]]~~	+
-	~~[[Category: Protein complex]]~~	+
-	~~[[Category: Coller, B S.]]~~	+
-	~~[[Category: Springer, T A.]]~~	+
-	~~[[Category: Takagi, J.]]~~	+
-	~~[[Category: Wang, J H.]]~~	+
-	~~[[Category: Xiao, T.]]~~	+
-	~~[[Category: Allostery]]~~	+
-	~~[[Category: Crystal structure]]~~	+
-	~~[[Category: Fibrinogen binding]]~~	+
-	~~[[Category: Platelet integrin alphaiibbeta3]]~~	+
-	~~[[Category: Therapeutic antagonism]]~~	+
-		+
-	~~''Page seeded~~ by ~~[http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 03:44:31 2008''~~	+

OCA at 00:44, 29 July 2008

OCA — Tue, 29 Jul 2008 00:44:34 GMT

←Older revision		Revision as of 00:44, 29 July 2008
Line 1:		Line 1:
-	[[Image:1txv.~~gif~~\|left\|200px]]	+	{{Seed}}
		+	[[Image:1txv.png\|left\|200px]]

	<!--		<!--
Line 9:		Line 10:
	{{STRUCTURE_1txv\| PDB=1txv \| SCENE= }}		{{STRUCTURE_1txv\| PDB=1txv \| SCENE= }}

-	~~'''~~Structural basis for allostery in integrins and binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen~~'''~~	+	===Structural basis for allostery in integrins and binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen===


-	~~==Overview==~~	+	<!--
-	Integrins are important adhesion receptors in all Metazoa that transmit conformational change bidirectionally across the membrane. Integrin alpha and beta subunits form a head and two long legs in the ectodomain and span the membrane. Here, ~~we define with crystal structures~~ the ~~atomic basis for allosteric regulation of~~ the ~~conformation and affinity for ligand of the integrin ectodomain, and how fibrinogen-mimetic therapeutics bind to platelet integrin alpha~~(~~IIb)beta3~~. ~~Allostery in the beta3 I domain alters three metal binding sites, associated loops and alpha1- and alpha7-helices~~. ~~Piston-like displacement of the alpha7-helix causes a 62 degrees reorientation between the beta3 I and hybrid domains. Transmission through the rigidly connected plexin/semaphorin/integrin (PSI~~) ~~domain in~~ the ~~upper beta3 leg causes a 70 A separation between the knees of the alpha and beta legs~~. ~~Allostery in the head thus disrupts interaction between the legs in a previously described low~~-~~affinity bent integrin conformation, and leg extension positions the high~~-~~affinity head far above the cell surface.~~	+	The line below this paragraph, {{ABSTRACT_PUBMED_15378069}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 15378069 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_15378069}}

	==About this Structure==		==About this Structure==
Line 33:		Line 37:
	[[Category: Platelet integrin alphaiibbeta3]]		[[Category: Platelet integrin alphaiibbeta3]]
	[[Category: Therapeutic antagonism]]		[[Category: Therapeutic antagonism]]
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sat May 3 10~~:30:10 2008''	+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 03:44:31 2008''

OCA at 07:30, 3 May 2008

OCA — Sat, 03 May 2008 07:30:11 GMT

←Older revision		Revision as of 07:30, 3 May 2008
Line 1:		Line 1:
	[[Image:1txv.gif\|left\|200px]]		[[Image:1txv.gif\|left\|200px]]

-	~~{{Structure~~	+	<!--
-	~~\|PDB= 1txv \|SIZE=350\|CAPTION=~~ <~~scene name='initialview01'>1txv</scene>, resolution 2.75Å~~	+	The line below this paragraph, containing "STRUCTURE_1txv", creates the "Structure Box" on the page.
-	~~\|SITE=~~	+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	~~\|LIGAND= <scene name='pdbligand=BMA:BETA~~-D-~~MANNOSE'>BMA</scene>~~, ~~<scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>~~, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(~~ACETYLAMINO~~)~~-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>~~	+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	~~\|ACTIVITY=~~	+	or leave the SCENE parameter empty for the default display.
-	~~\|GENE= ITGAB~~ (~~[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]~~)	+	-->
-	~~\|DOMAIN=~~	+	{{STRUCTURE_1txv\| PDB=1txv \| SCENE= }}
-	~~\|RELATEDENTRY=[[1ty3\|1TY3]]~~, ~~[[1ty5\|1TY5]], [[1ty6\|1TY6]], [[1ty7\|1TY7]], [[1tye\|1TYE]]~~	+
-	~~\|RESOURCES=<span class='plainlinks'>[http://oca~~.~~weizmann.ac.il/oca~~-~~docs/fgij/fg.htm?mol=1txv FirstGlance], [http://oca.weizmann.ac.il/oca~~-~~bin/ocaids?id~~=1txv ~~OCA], [http://www.ebi.ac.uk/pdbsum/1txv PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId~~=~~1txv RCSB]</span>~~	+
-	}}	+

	'''Structural basis for allostery in integrins and binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen'''		'''Structural basis for allostery in integrins and binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen'''
Line 31:		Line 28:
	[[Category: Wang, J H.]]		[[Category: Wang, J H.]]
	[[Category: Xiao, T.]]		[[Category: Xiao, T.]]
-	[[Category: ~~allostery~~]]	+	[[Category: Allostery]]
-	[[Category: ~~crystal~~ structure]]	+	[[Category: Crystal structure]]
-	[[Category: ~~fibrinogen~~ binding]]	+	[[Category: Fibrinogen binding]]
-	[[Category: ~~platelet~~ integrin alphaiibbeta3]]	+	[[Category: Platelet integrin alphaiibbeta3]]
-	[[Category: ~~therapeutic~~ antagonism]]	+	[[Category: Therapeutic antagonism]]
-		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:30:10 2008''
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Mon Mar 31 00~~:02:37 2008''	+

OCA at 21:02, 30 March 2008

OCA — Sun, 30 Mar 2008 21:02:41 GMT

←Older revision		Revision as of 21:02, 30 March 2008
Line 4:		Line 4:
	\|PDB= 1txv \|SIZE=350\|CAPTION= <scene name='initialview01'>1txv</scene>, resolution 2.75Å		\|PDB= 1txv \|SIZE=350\|CAPTION= <scene name='initialview01'>1txv</scene>, resolution 2.75Å
	\|SITE=		\|SITE=
-	\|LIGAND= <scene name='pdbligand=~~NAG~~:~~N-ACETYL~~-D-~~GLUCOSAMINE~~'>~~NAG~~</scene>, <scene name='pdbligand=~~NDG~~:~~2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE~~'>~~NDG~~</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=CA:~~CALCIUM+ION~~'>CA</scene> ~~and~~ <scene name='pdbligand=~~GOL~~:~~GLYCEROL~~'>~~GOL~~</scene>	+	\|LIGAND= <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>
	\|ACTIVITY=		\|ACTIVITY=
	\|GENE= ITGAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])		\|GENE= ITGAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
		+	\|DOMAIN=
		+	\|RELATEDENTRY=[[1ty3\|1TY3]], [[1ty5\|1TY5]], [[1ty6\|1TY6]], [[1ty7\|1TY7]], [[1tye\|1TYE]]
		+	\|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1txv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1txv OCA], [http://www.ebi.ac.uk/pdbsum/1txv PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1txv RCSB]</span>
	}}		}}

Line 14:		Line 17:
	==Overview==		==Overview==
	Integrins are important adhesion receptors in all Metazoa that transmit conformational change bidirectionally across the membrane. Integrin alpha and beta subunits form a head and two long legs in the ectodomain and span the membrane. Here, we define with crystal structures the atomic basis for allosteric regulation of the conformation and affinity for ligand of the integrin ectodomain, and how fibrinogen-mimetic therapeutics bind to platelet integrin alpha(IIb)beta3. Allostery in the beta3 I domain alters three metal binding sites, associated loops and alpha1- and alpha7-helices. Piston-like displacement of the alpha7-helix causes a 62 degrees reorientation between the beta3 I and hybrid domains. Transmission through the rigidly connected plexin/semaphorin/integrin (PSI) domain in the upper beta3 leg causes a 70 A separation between the knees of the alpha and beta legs. Allostery in the head thus disrupts interaction between the legs in a previously described low-affinity bent integrin conformation, and leg extension positions the high-affinity head far above the cell surface.		Integrins are important adhesion receptors in all Metazoa that transmit conformational change bidirectionally across the membrane. Integrin alpha and beta subunits form a head and two long legs in the ectodomain and span the membrane. Here, we define with crystal structures the atomic basis for allosteric regulation of the conformation and affinity for ligand of the integrin ectodomain, and how fibrinogen-mimetic therapeutics bind to platelet integrin alpha(IIb)beta3. Allostery in the beta3 I domain alters three metal binding sites, associated loops and alpha1- and alpha7-helices. Piston-like displacement of the alpha7-helix causes a 62 degrees reorientation between the beta3 I and hybrid domains. Transmission through the rigidly connected plexin/semaphorin/integrin (PSI) domain in the upper beta3 leg causes a 70 A separation between the knees of the alpha and beta legs. Allostery in the head thus disrupts interaction between the legs in a previously described low-affinity bent integrin conformation, and leg extension positions the high-affinity head far above the cell surface.
-
-	==Disease==
-	Known diseases associated with this structure: Glanzmann thrombasthenia, type A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607759 607759]], Glanzmann thrombasthenia, type B OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173470 173470]], Thrombocytopenia, neonatal alloimmune OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607759 607759]]

	==About this Structure==		==About this Structure==
Line 31:		Line 31:
	[[Category: Wang, J H.]]		[[Category: Wang, J H.]]
	[[Category: Xiao, T.]]		[[Category: Xiao, T.]]
-	[[Category: CA]]	+	[[Category: allostery]]
-	[[Category: ~~CAC~~]]	+	[[Category: crystal structure]]
-	[[Category: ~~GOL~~]]	+	[[Category: fibrinogen binding]]
-	[[Category: MG]]	+	[[Category: platelet integrin alphaiibbeta3]]
-	[[Category: ~~NAG]]~~	+	[[Category: therapeutic antagonism]]
-	~~[[Category: NDG]]~~	+
-	~~[[Category: crystal structure; platelet integrin alphaiibbeta3; fibrinogen binding; allostery;~~ therapeutic antagonism]]	+

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Thu~~ Mar ~~20 14~~:24:38 2008''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:02:37 2008''

OCA at 12:24, 20 March 2008

OCA — Thu, 20 Mar 2008 12:24:39 GMT

←Older revision		Revision as of 12:24, 20 March 2008
Line 1:		Line 1:
-	[[Image:1txv.gif\|left\|200px]]~~<br /><applet load~~="1txv~~" size~~="350~~" color~~=~~"white" frame="true" align="right" spinBox="true"~~	+	[[Image:1txv.gif\|left\|200px]]
-	~~caption~~="1txv, resolution 2.75Å" />	+
-	'''Structural basis for allostery in integrins and binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen'''~~<br />~~	+	{{Structure
		+	\|PDB= 1txv \|SIZE=350\|CAPTION= <scene name='initialview01'>1txv</scene>, resolution 2.75Å
		+	\|SITE=
		+	\|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
		+	\|ACTIVITY=
		+	\|GENE= ITGAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
		+	}}
		+
		+	'''Structural basis for allostery in integrins and binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen'''
		+

	==Overview==		==Overview==
Line 10:		Line 19:

	==About this Structure==		==About this Structure==
-	1TXV is a [~~http://en.wikipedia.org/wiki/Protein_complex~~ Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=NDG:'>NDG</scene>, <scene name='pdbligand=CAC:'>CAC</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TXV OCA].	+	1TXV is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TXV OCA].

	==Reference==		==Reference==
-	Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics., Xiao T, Takagi J, Coller BS, Wang JH, Springer TA, Nature. 2004 Nov 4;432(7013):59-67. Epub 2004 Sep 19. PMID:[http://~~ispc~~.~~weizmann~~.ac.~~il/~~/~~pmbin~~/~~getpm?pmid=~~15378069 15378069]	+	Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics., Xiao T, Takagi J, Coller BS, Wang JH, Springer TA, Nature. 2004 Nov 4;432(7013):59-67. Epub 2004 Sep 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15378069 15378069]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
Line 30:		Line 39:
	[[Category: crystal structure; platelet integrin alphaiibbeta3; fibrinogen binding; allostery; therapeutic antagonism]]		[[Category: crystal structure; platelet integrin alphaiibbeta3; fibrinogen binding; allostery; therapeutic antagonism]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu ~~Feb 21 15~~:18:30 2008''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:24:38 2008''

OCA at 13:18, 21 February 2008

OCA — Thu, 21 Feb 2008 13:18:32 GMT

←Older revision		Revision as of 13:18, 21 February 2008
Line 1:		Line 1:
-	[[Image:1txv.gif\|left\|200px]]<br />	+	[[Image:1txv.gif\|left\|200px]]<br /><applet load="1txv" size="350" color="white" frame="true" align="right" spinBox="true"
-	<applet load="1txv" size="~~450~~" color="white" frame="true" align="right" spinBox="true"	+
	caption="1txv, resolution 2.75Å" />		caption="1txv, resolution 2.75Å" />
	'''Structural basis for allostery in integrins and binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen'''<br />		'''Structural basis for allostery in integrins and binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen'''<br />

	==Overview==		==Overview==
-	Integrins are important adhesion receptors in all Metazoa that transmit, conformational change bidirectionally across the membrane. Integrin alpha, and beta subunits form a head and two long legs in the ectodomain and span, the membrane. Here, we define with crystal structures the atomic basis for, allosteric regulation of the conformation and affinity for ligand of the, integrin ectodomain, and how fibrinogen-mimetic therapeutics bind to, platelet integrin alpha(IIb)beta3. Allostery in the beta3 I domain alters, three metal binding sites, associated loops and alpha1- and, alpha7-helices. Piston-like displacement of the alpha7-helix causes a 62, degrees reorientation between the beta3 I and hybrid domains. Transmission, through the rigidly connected plexin/semaphorin/integrin (PSI) domain in, the upper beta3 leg causes a 70 A separation between the knees of the, alpha and beta legs. Allostery in the head thus disrupts interaction, between the legs in a previously described low-affinity bent integrin, conformation, and leg extension positions the high-affinity head far above, the cell surface.	+	Integrins are important adhesion receptors in all Metazoa that transmit conformational change bidirectionally across the membrane. Integrin alpha and beta subunits form a head and two long legs in the ectodomain and span the membrane. Here, we define with crystal structures the atomic basis for allosteric regulation of the conformation and affinity for ligand of the integrin ectodomain, and how fibrinogen-mimetic therapeutics bind to platelet integrin alpha(IIb)beta3. Allostery in the beta3 I domain alters three metal binding sites, associated loops and alpha1- and alpha7-helices. Piston-like displacement of the alpha7-helix causes a 62 degrees reorientation between the beta3 I and hybrid domains. Transmission through the rigidly connected plexin/semaphorin/integrin (PSI) domain in the upper beta3 leg causes a 70 A separation between the knees of the alpha and beta legs. Allostery in the head thus disrupts interaction between the legs in a previously described low-affinity bent integrin conformation, and leg extension positions the high-affinity head far above the cell surface.

	==Disease==		==Disease==
Line 11:		Line 10:

	==About this Structure==		==About this Structure==
-	1TXV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NAG, NDG, CAC, MG, CA and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1TXV OCA].	+	1TXV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=NDG:'>NDG</scene>, <scene name='pdbligand=CAC:'>CAC</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TXV OCA].

	==Reference==		==Reference==
Line 18:		Line 17:
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Protein complex]]		[[Category: Protein complex]]
-	[[Category: Coller, B.S.]]	+	[[Category: Coller, B S.]]
-	[[Category: Springer, T.A.]]	+	[[Category: Springer, T A.]]
	[[Category: Takagi, J.]]		[[Category: Takagi, J.]]
-	[[Category: Wang, J.H.]]	+	[[Category: Wang, J H.]]
	[[Category: Xiao, T.]]		[[Category: Xiao, T.]]
	[[Category: CA]]		[[Category: CA]]
Line 31:		Line 30:
	[[Category: crystal structure; platelet integrin alphaiibbeta3; fibrinogen binding; allostery; therapeutic antagonism]]		[[Category: crystal structure; platelet integrin alphaiibbeta3; fibrinogen binding; allostery; therapeutic antagonism]]

-	''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 19~~:29:~~16 2007~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:18:30 2008''

OCA: New page: 200px
'''Structural basis fo...
OCA — Mon, 12 Nov 2007 17:22:50 GMT

New page: 200px<br /> <applet load="1txv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1txv, resolution 2.75Å" /> '''Structural basis fo...

New page
[[Image:1txv.gif|left|200px]]<br />
<applet load="1txv" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1txv, resolution 2.75Å" />
'''Structural basis for allostery in integrins and binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen'''<br />

==Overview==
Integrins are important adhesion receptors in all Metazoa that transmit, conformational change bidirectionally across the membrane. Integrin alpha, and beta subunits form a head and two long legs in the ectodomain and span, the membrane. Here, we define with crystal structures the atomic basis for, allosteric regulation of the conformation and affinity for ligand of the, integrin ectodomain, and how fibrinogen-mimetic therapeutics bind to, platelet integrin alpha(IIb)beta3. Allostery in the beta3 I domain alters, three metal binding sites, associated loops and alpha1- and, alpha7-helices. Piston-like displacement of the alpha7-helix causes a 62, degrees reorientation between the beta3 I and hybrid domains. Transmission, through the rigidly connected plexin/semaphorin/integrin (PSI) domain in, the upper beta3 leg causes a 70 A separation between the knees of the, alpha and beta legs. Allostery in the head thus disrupts interaction, between the legs in a previously described low-affinity bent integrin, conformation, and leg extension positions the high-affinity head far above, the cell surface.

==Disease==
Known diseases associated with this structure: Glanzmann thrombasthenia, type A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607759 607759]], Glanzmann thrombasthenia, type B OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173470 173470]], Thrombocytopenia, neonatal alloimmune OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607759 607759]]

==About this Structure==
1TXV is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NAG, NDG, CAC, MG, CA and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TXV OCA].

==Reference==
Structural basis for allostery in integrins and binding to fibrinogen-mimetic therapeutics., Xiao T, Takagi J, Coller BS, Wang JH, Springer TA, Nature. 2004 Nov 4;432(7013):59-67. Epub 2004 Sep 19. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15378069 15378069]
[[Category: Homo sapiens]]
[[Category: Mus musculus]]
[[Category: Protein complex]]
[[Category: Coller, B.S.]]
[[Category: Springer, T.A.]]
[[Category: Takagi, J.]]
[[Category: Wang, J.H.]]
[[Category: Xiao, T.]]
[[Category: CA]]
[[Category: CAC]]
[[Category: GOL]]
[[Category: MG]]
[[Category: NAG]]
[[Category: NDG]]
[[Category: crystal structure; platelet integrin alphaiibbeta3; fibrinogen binding; allostery; therapeutic antagonism]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:29:16 2007''