We have expressed two proteins that correspond to the transmembrane and cytoplasmic domains of integrin αIIb and β3 subunits. Characterization of these proteins, dispersed in anionic and zwitterionic micelles, revealed that, rather than interacting with each other, the two proteins associated into homodimers and homotrimers respectively. Moreover, studies using the TOXCAT assay system confirmed that the αIIb and β3 transmembrane domains can self-associate in biological cell membranes. Transmembrane domain-mediated homo-oligomerization provides a plausible structural basis for integrin clustering and could promote integrin activation as well. Indeed, replacing specific residues in the transmembrane helix of either αIIb or β3 with an asparagine residue resulted in a facilitated homo-oligomerization of the mutated transmembrane helix, promoted the formation of integrin clusters on the cell surface and shifted αIIbβ3 to its activated state. Thus these studies support the hypothesis that the transmembrane domains play a vital role in the function and regulation of αIIbβ3.
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Conference Article|
June 01 2004
Structural basis for integrin αIIbβ3 clustering
R. Li;
R. Li
1
*Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
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J.S. Bennett;
J.S. Bennett
2
†The Hematology–Oncology Division, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
2Correspondence may be addressed to either author (email bennetts@mail.med.upenn.edu or wdegrado@mail.med.upenn.edu).
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W.F. DeGrado
W.F. DeGrado
2
*Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
2Correspondence may be addressed to either author (email bennetts@mail.med.upenn.edu or wdegrado@mail.med.upenn.edu).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2004 Biochemical Society
2004
Biochem Soc Trans (2004) 32 (3): 412–415.
Citation
R. Li, J.S. Bennett, W.F. DeGrado; Structural basis for integrin αIIbβ3 clustering. Biochem Soc Trans 1 June 2004; 32 (3): 412–415. doi: https://doi.org/10.1042/bst0320412
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