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Structural Elucidation of Integrin αIIbβ3 Cytoplasmic Domain by Nuclear Magnetic Resonance Spectroscopy

Part of the Methods in Molecular Medicine book series (MIMM, volume 129)

Abstract

Integrin αIIbβ3 is a heterodimeric (α/β) cell surface receptor critical for platelet aggregation, and its dysfunction is linked to thrombosis and a number of other vascular diseases. Upon agonist stimulation, which leads to platelet aggregation, αIIbβ3 is activated via a distinct inside-out signaling pathway, i.e., the short αIIb3 cytoplasmic tails receive intracellular signals, which trigger the conformational change of the extracellular domain for the high-affinity ligand binding. The structural basis for how the αIIbβ3 cytoplasmic face regulates the inside-out activation of the receptor has been extensively studied over the past decade. We have recently used nuclear magnetic resonance (NMR) spectroscopy to characterize and determine the structural features of the αIIbβ3 cytoplasmic domain. This chapter describes detailed practical procedures for performing these NMR studies, which have provided key atomic insights into the mechanism of the αIIbβ3 function, especially its inside-out signaling.

Key Words

Integrin cytoplasmic domain platelet aggregation NMR 

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Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Jun Qin
    • 1
  1. 1.Structural Biology ProgramThe Cleveland Clinic FoundationCleveland

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