1s4w: Difference between revisions
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= ITGA2B, ITGAB, GP2B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= ITGA2B, ITGAB, GP2B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1s4x|1S4X]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1s4w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s4w OCA], [http://www.ebi.ac.uk/pdbsum/1s4w PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1s4w RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Cytoplasmic face-mediated integrin inside-out activation remains a paradigm in transmembrane signal transduction. Emerging evidence suggests that this process involves dissociation of the complex between the integrin cytoplasmic tails; however, a dynamic image of how it occurs on the membrane surface remains elusive. We show here that, whereas membrane-proximal helices of integrin alpha/beta cytoplasmic tails associate in cytoplasm-like aqueous medium, they become partially embedded into membrane-mimetic micelles when unclasped. Membrane embedding induces substantial structural changes of the cytoplasmic tails as compared to their aqueous conformations and suggests there may be an upward movement of the membrane-proximal helices into the membrane during their separation. We further demonstrate that the beta3 tail exhibits additional membrane binding site at its C terminus containing the NPLY motif. Talin, a key intracellular integrin activator, recognizes this site as well as the membrane-proximal helix, thereby promoting cytoplasmic tail separation along the membrane surface. These data provide a structural basis of membrane-mediated changes at the cytoplasmic face in regulating integrin activation and signaling. | Cytoplasmic face-mediated integrin inside-out activation remains a paradigm in transmembrane signal transduction. Emerging evidence suggests that this process involves dissociation of the complex between the integrin cytoplasmic tails; however, a dynamic image of how it occurs on the membrane surface remains elusive. We show here that, whereas membrane-proximal helices of integrin alpha/beta cytoplasmic tails associate in cytoplasm-like aqueous medium, they become partially embedded into membrane-mimetic micelles when unclasped. Membrane embedding induces substantial structural changes of the cytoplasmic tails as compared to their aqueous conformations and suggests there may be an upward movement of the membrane-proximal helices into the membrane during their separation. We further demonstrate that the beta3 tail exhibits additional membrane binding site at its C terminus containing the NPLY motif. Talin, a key intracellular integrin activator, recognizes this site as well as the membrane-proximal helix, thereby promoting cytoplasmic tail separation along the membrane surface. These data provide a structural basis of membrane-mediated changes at the cytoplasmic face in regulating integrin activation and signaling. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: cell adhesion]] | [[Category: cell adhesion]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:37:24 2008'' | ||
Revision as of 23:37, 30 March 2008
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| Gene: | ITGA2B, ITGAB, GP2B (Homo sapiens) | ||||||
| Related: | 1S4X
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NMR structure of the cytoplasmic domain of integrin AIIb in DPC micelles
OverviewOverview
Cytoplasmic face-mediated integrin inside-out activation remains a paradigm in transmembrane signal transduction. Emerging evidence suggests that this process involves dissociation of the complex between the integrin cytoplasmic tails; however, a dynamic image of how it occurs on the membrane surface remains elusive. We show here that, whereas membrane-proximal helices of integrin alpha/beta cytoplasmic tails associate in cytoplasm-like aqueous medium, they become partially embedded into membrane-mimetic micelles when unclasped. Membrane embedding induces substantial structural changes of the cytoplasmic tails as compared to their aqueous conformations and suggests there may be an upward movement of the membrane-proximal helices into the membrane during their separation. We further demonstrate that the beta3 tail exhibits additional membrane binding site at its C terminus containing the NPLY motif. Talin, a key intracellular integrin activator, recognizes this site as well as the membrane-proximal helix, thereby promoting cytoplasmic tail separation along the membrane surface. These data provide a structural basis of membrane-mediated changes at the cytoplasmic face in regulating integrin activation and signaling.
About this StructureAbout this Structure
1S4W is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Membrane-mediated structural transitions at the cytoplasmic face during integrin activation., Vinogradova O, Vaynberg J, Kong X, Haas TA, Plow EF, Qin J, Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4094-9. Epub 2004 Mar 15. PMID:15024114
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