A computational model of transmembrane integrin clustering.
The presented work describes a structural model for integrin homooligomerization, focusing on the transmembrane domains. The two noncovalently linked integrin subunits, alpha and beta, were previously shown to homodimerize or homotrimerize, respectively. Our work is based on published mutational work that induced homotrimerization of beta3 integrins. The mutations provided structural restraints for the creation of a structural model of the beta3 homotrimer by a computational search of the conformational space of homomeric interactions of the beta3 integrin. Additionally, we explored possible conformations of the alphaIIb integrin homodimer, for which no unique solution was found. Two possible models of signal transduction, involving two different alphaIIb conformations, are discussed. One of the possible homodimeric alphaIIb conformations is GpA like, which is in line with experimental evidence. Based on our here-presented structural models and on recent experiments, we will argue that most probably the heteromeric alpha/beta transmembrane complex separates in the course of clustering.
Gottschalk
Kay-Eberhard
KE
Department of Biological Chemistry, Weizmann Institute of Science, Herzl Street 1, 76100 Rehovot, Israel. kay-gottschalk@weizmann.ac.il
Kessler
Horst
H
D020816:Amino Acid Motifs; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D004252:DNA Mutational Analysis; D019281:Dimerization; D006021:Glycophorins / Q000737:chemistry; D006801:Humans; D016023:Integrins / Q000737:chemistry*; D009154:Mutation; D011487:Protein Conformation; D015398:Signal Transduction; D012984:Software
D006021:Glycophorins; D016023:Integrins