1tye: Difference between revisions

Revision as of 10:31, 3 May 2008

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

OverviewOverview

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 StructureAbout this Structure

1TYE is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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:15378069 Page seeded by OCA on Sat May 3 10:31:16 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1tye.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1tye |SIZE=350|CAPTION= <scene name='initialview01'>1tye</scene>, resolution 2.90&Aring;
+The line below this paragraph, containing "STRUCTURE_1tye", 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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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_1tye|  PDB=1tye  |  SCENE=  }}
-|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>
-}}
 '''Structural basis for allostery in integrins and binding of ligand-mimetic therapeutics to the platelet receptor for fibrinogen'''
@@ Line 30: / Line 27: @@
 [[Category: Wang, J H.]]
 [[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 10:31:16 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:02:51 2008''