On the formation of ordered protein assemblies in cell-cell contact

Cell adhesion receptors mediate cell-cell recognition and adhesion, and trigger signaling pathways responsible for specification of synaptic connectivity. High resolution structures of these proteins and their assemblies provide both mechanistic insights into recognition specificities and crucial insights into the physical architectural features required for signaling integration. These structures indicate that many adhesion proteins assemble in a linear array (zipper-like array) because of networks of cis (i.e., same cell) and trans (i.e., contacting cells) interactions. I will present a computational model to simulate the formation of oligomers of adhesion proteins between contacting cells using a simplified yet realistic representation of these protein structures. Our results, published recently in PNAS, reveal that the formation of long linear protein assemblies is an implicit feature of these structures and is driven by their cis and trans interactions. Moreover, even in the absence of interactions between individual arrays, the zippers appear to organize into an ordered two-dimensional arrays. Our results suggest that adhesion proteins observed, in crystal structures, to be arranged in one-dimension zippers are likely to form ordered two-dimension assemblies in cell-cell contact region.