Document Type

Article

Publication Date

4-24-2009

Abstract

Structures of intact receptors with single-pass transmembrane domains are essential to understand how extracellular and cytoplasmic domains regulate association and signaling through transmembrane domains. A chemical and computational method to determine structures of the membrane regions of such receptors on the cell surface is developed here and validated with glycophorin A. An integrin heterodimer structure reveals association over most of the lengths of the α and β transmembrane domains and shows that the principles governing association of hetero and homo transmembrane dimers differ. A turn at the Gly of the juxtamembrane GFFKR motif caps the α TM helix and brings the two Phe of GFFKR into the α/β interface. A juxtamembrane Lys residue in β also has an important role in the interface. The structure shows how transmembrane association/dissociation regulates integrin signaling. A joint ectodomain and membrane structure shows that substantial flexibility between the extracellular and TM domains is compatible with TM signaling. © 2009 Elsevier Inc. All rights reserved.

Publication Source (Journal or Book title)

Molecular Cell

First Page

234

Last Page

249

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