Evidence for hetero-association of transmembrane helices of integrins

Integrins are important transmembrane cell-surface receptors, which mediate interactions of the cell with other cells or the extracellular matrix. Integrins are heterodimers composed of an alpha- and a beta-subunit. They can switch between different activation states depending on intra- or extracellular signals. Inside/out and outside/in signaling is mediated via integrins across the membrane. A biologically important and yet still unanswered question is the role of the transmembrane domains in the signaling event. Here it is shown by simulated annealing/molecular dynamics calculations that recently published structural data of the cytoplasmic domains of integrin alphaIIbbeta3 are supporting a structure with interacting transmembrane helices. This corroborates a model of transmembrane domains that are actively involved in the transmembrane signaling event. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.