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IIbß3 integrin
1 Institut für Organische Chemie und Biochemie, Technische Universität München, München, Germany
2 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA
Reprint requests to: Horst Kessler, Technische Universität München, Institut für Organische Chemie und Biochemie, Lichtenbergstr. 4, D-85747 Garching, Germany; e-mail: horst.kessler{at}ch.tum.de; fax: 49-89-289-13210.
Integrins are composed of noncovalently bound dimers of an 
- and a ß-subunit. They play an important role in cell-matrix adhesion and signal transduction through the cell membrane. Signal transduction can be initiated by the binding of intracellular proteins to the integrin. Binding leads to a major conformational change. The change is passed on to the extracellular domain through the membrane. The affinity of the extracellular domain to certain ligands increases; thus at least two states exist, a low-affinity and a high-affinity state. The conformations and conformational changes of the transmembrane (TM) domain are the focus of our interest. We show by a global search of helix–helix interactions that the TM section of the family of integrins are capable of adopting a structure similar to the structure of the homodimeric TM protein Glycophorin A. For the IIbß3 integrin, this structural motif represents the high-affinity state. A second conformation of the TM domain of IIbß3 is identified as the low-affinity state by known mutational and nuclear magnetic resonance (NMR) studies. A transition between these two states was determined by molecular dynamics (MD) calculations. On the basis of these calculations, we propose a three-state mechanism.
Keywords: Signal transduction; molecular modeling; integrin; glycophorin A; transmembrane
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