1s4x
NMR Structure of the integrin B3 cytoplasmic domain in DPC micelles
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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.
DiseaseDisease
Known diseases associated with this structure: Glanzmann thrombasthenia, type B OMIM:[173470]
About this StructureAbout this Structure
1S4X 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
Page seeded by OCA on Mon Nov 12 19:10:33 2007