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, α and β, were previously shown to homodimerize or homotrimerize, respectively. Our work is based on published mutational work that induced homotrimerization of β3 integrins. The mutations provided structural restraints for the creation of a structural model of the β3 homotrimer by a computational search of the conformational space of homomeric interactions of the β3 integrin. Additionally, we explored possible conformations of the αIIb integrin homodimer, for which no unique solution was found. Two possible models of signal transduction, involving two different αIIb conformations, are discussed. One of the possible homodimeric αIIb 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 α/β transmembrane complex separates in the course of clustering.