Protein-Protein Complexes

Abstract

Protein-protein complexes are prevalent in living systems and are central to the way biological processes function. Several of these complexes have been crystallized and their structures and functions characterized, while a much larger number of them (that may not crystallize) operate in the physiological system. Analyses of the known structures of proteinprotein complexes reveal that they form through interactions between specific patches on the surface of the component proteins. These patches, called interacting domains, are made from mostly non-contiguous residues in the protein sequence. Not all, but only a few of these residues called “hot spots”, contribute significantly to the binding free energy of these complexes. Interactions between the hot spot residues from two interacting domains control the thermodynamics and oligomeric states of the complexes. The hot spot residues have been targets for the design of small molecule agonists with medicinal applications. The interaction domains in protein-protein complexes vary in their contour, size, shape, complementarity and affinity. The number of interacting protomers in a complex can vary from 2 to >30. These complexes have been classified based on the 3-dimensional architecture, binding energies and lifetimes of these quaternary assemblies and the presence of symmetry in their structure. Protein-protein complexes have evolved to perform and regulate activities like signal transduction, metabolism, cell division and controlled cell death, in response to specific stimuli. These functions are outside the capacity of monomeric proteins. In this review, an overview of these features is discussed with an emphasis on the structures and intermolecular interactions in these complexes.