The role of ubiquitin in many of the known cellular processes, not just protein degradation, is based on its unique ability to bind a range of proteins that are structurally and functionally different. To understand how ubiquitin can bind to proteins with different structures, we review the extent of the conservation and variation that occur in the structures of two free ubiquitins and ubiquitins in 16 complexes that have been determined at high resolution (1.2-2A). Around 80% of the atomic groups in these structures have positions that differ less than 1A. This conserved core provides a rigid platform for flexible loop regions, 39 residues with side chains that can take up different conformations, and a flexible six-residue region at the C-terminus. In most cases the ability of ubiquitin to bind different structures is limited in part by a central set of residues that largely conserve their conformations. The accommodation of differences in binding proteins is enabled by changes in the flexible surface side chains, loop movements, different specific interactions, water molecules in the interface and the flexible C-terminus.
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