1DPQ

SOLUTION STRUCTURE OF THE CONSTITUTIVELY ACTIVE MUTANT OF THE INTEGRIN ALPHA IIB CYTOPLASMIC DOMAIN.

Summary for 1DPQ

• Entry DOI: 10.2210/pdb1dpq/pdb
• Related: 1DPK
• Descriptor: INTEGRIN ALPHA-IIB SUBUNIT (1 entity in total)
• Functional Keywords: helix, cell adhesion
• Cellular location: Membrane; Single-pass type I membrane protein: P08514
• Total number of polymer chains: 1
• Total formula weight: 2343.51

Authors

Vinogradova, O.,Haas, T.,Plow, E.F.,Qin, J. (deposition date: 1999-12-27, release date: 2000-02-28, Last modification date: 2024-05-22)

Primary citation

Vinogradova, O.,Haas, T.,Plow, E.F.,Qin, J.
A structural basis for integrin activation by the cytoplasmic tail of the alpha IIb-subunit.
Proc.Natl.Acad.Sci.USA, 97:1450-1455, 2000

PubMed Abstract: 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.

PubMed: 10677482
DOI: 10.1073/pnas.040548197

Experimental method

SOLUTION NMR