1tye: Difference between revisions
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|PDB= 1tye |SIZE=350|CAPTION= <scene name='initialview01'>1tye</scene>, resolution 2.90Å | |PDB= 1tye |SIZE=350|CAPTION= <scene name='initialview01'>1tye</scene>, resolution 2.90Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand= | |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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=[[1txv|1TXV]], [[1ty3|1TY3]], [[1ty5|1TY5]], [[1ty6|1TY6]], [[1ty7|1TY7]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tye OCA], [http://www.ebi.ac.uk/pdbsum/1tye PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1tye RCSB]</span> | |||
}} | }} | ||
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==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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Wang, J H.]] | [[Category: Wang, J H.]] | ||
[[Category: Xiao, T.]] | [[Category: Xiao, T.]] | ||
[[Category: | [[Category: allostery]] | ||
[[Category: | [[Category: crystal structure]] | ||
[[Category: | [[Category: fibrinogen binding]] | ||
[[Category: | [[Category: platelet integrin alphaiibbeta3]] | ||
[[Category: | [[Category: therapeutic antagonism]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:02:51 2008'' | ||