1ty7: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 4: Line 4:
|PDB= 1ty7 |SIZE=350|CAPTION= <scene name='initialview01'>1ty7</scene>, resolution 3.10&Aring;
|PDB= 1ty7 |SIZE=350|CAPTION= <scene name='initialview01'>1ty7</scene>, resolution 3.10&Aring;
|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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=180:2-(S)-[N-(3-PYRIDYLSULFONYL)AMINO]-3-[[2-CARBONYL-5-[2-(PIPERIDIN-4-YL)ETHYL]-THIENO[2,3-B]THIOPHENEYL]AMINO]-PROPIONIC+ACID'>180</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
|LIGAND= <scene name='pdbligand=180:2-(S)-[N-(3-PYRIDYLSULFONYL)AMINO]-3-[[2-CARBONYL-5-[2-(PIPERIDIN-4-YL)ETHYL]-THIENO[2,3-B]THIOPHENEYL]AMINO]-PROPIONIC+ACID'>180</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=[[1txv|1TXV]], [[1ty3|1TY3]], [[1ty5|1TY5]], [[1ty6|1TY6]], [[1tye|1TYE]]
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ty7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ty7 OCA], [http://www.ebi.ac.uk/pdbsum/1ty7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ty7 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: 180]]
[[Category: allostery]]
[[Category: CA]]
[[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 14:24:44 2008''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:02:47 2008''

Revision as of 00:02, 31 March 2008

File:1ty7.gif


PDB ID 1ty7

Drag the structure with the mouse to rotate
, resolution 3.10Å
Ligands: , , , , , , ,
Gene: ITGAB (Homo sapiens)
Related: 1TXV, 1TY3, 1TY5, 1TY6, 1TYE


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



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

1TY7 is a Protein complex structure of sequences from Homo sapiens and Mus musculus. 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 Mon Mar 31 00:02:47 2008

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

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=1ty7&oldid=273414"