title: Protein-protein interactions in clathrin vesicular assembly: radial distribution of evolutionary constraints in interfaces.
abstract: In eukaryotic organisms clathrin-coated vesicles are instrumental in the processes of endocytosis as well as intracellular protein trafficking. Hence, it is important to understand how these vesicles have evolved across eukaryotes, to carry cargo molecules of varied shapes and sizes. The intricate nature and functional diversity of the vesicles are maintained by numerous interacting protein partners of the vesicle system. However, to delineate functionally important residues participating in protein-protein interactions of the assembly is a daunting task as there are no high-resolution structures of the intact assembly available. The two cryoEM structures closely representing intact assembly were determined at very low resolution and provide positions of Cα atoms alone. In the present study, using the method developed by us earlier, we predict the protein-protein interface residues in clathrin assembly, taking guidance from the available low-resolution structures. The conservation status of these interfaces when investigated across eukaryotes, revealed a radial distribution of evolutionary constraints, i.e., if the members of the clathrin vesicular assembly can be imagined to be arranged in spherical manner, the cargo being at the center and clathrins being at the periphery, the detailed phylogenetic analysis of these members of the assembly indicated high-residue variation in the members of the assembly closer to the cargo while high conservation was noted in clathrins and in other proteins at the periphery of the vesicle. This points to the strategy adopted by the nature to package diverse proteins but transport them through a highly conserved mechanism.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India. rupali@mbu.iisc.ernet.in
authors.forename: Rupali A
authors.initials: RA
authors.lastname: Gadkari
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Srinivasan
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002417:Cattle; D002966:Clathrin / Q000737:chemistry*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D004705:Endocytosis; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D010802:Phylogeny; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D051381:Rats
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D015415:Biomarkers; D002966:Clathrin