1dpq
From Proteopedia
|
SOLUTION STRUCTURE OF THE CONSTITUTIVELY ACTIVE MUTANT OF THE INTEGRIN ALPHA IIB CYTOPLASMIC DOMAIN.
Contents |
Overview
A key step in the activation of heterodimeric integrin adhesion receptors, is the transmission of an agonist-induced cellular signal from the short, alpha- and/or beta-cytoplasmic tails to the extracellular domains of the, receptor. The structural details of how the cytoplasmic tails mediate such, an inside-out signaling process remain unclear. We report herein the NMR, structures of a membrane-anchored cytoplasmic tail of the, alpha(IIb)-subunit and of a mutant alpha(IIb)-cytoplasmic tail that, renders platelet integrin alpha(IIb)beta(3) constitutively active. The, structure of the wild-type alpha(IIb)-cytoplasmic tail reveals a "closed", conformation where the highly conserved N-terminal membrane-proximal, region forms an alpha-helix followed by a turn, and the acidic C-terminal, loop interacts with the N-terminal helix. The structure of the active, mutant is significantly different, having an "open" conformation where the, interactions between the N-terminal helix and C-terminal region are, abolished. Consistent with these structural differences, the two peptides, differ in function: the wild-type peptide suppressed alpha(IIb)beta(3), activation, whereas the mutant peptide did not. These results provide an, atomic explanation for extensive biochemical/mutational data and support a, conformation-based "on/off switch" model for integrin activation.
Disease
Known diseases associated with this structure: Glanzmann thrombasthenia, type A OMIM:[607759], Thrombocytopenia, neonatal alloimmune OMIM:[607759]
About this Structure
1DPQ is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
A structural basis for integrin activation by the cytoplasmic tail of the alpha IIb-subunit., Vinogradova O, Haas T, Plow EF, Qin J, Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1450-5. PMID:10677482
Page seeded by OCA on Fri Feb 15 15:40:30 2008
