Structure and Function of a novel and pervasive Ubiqitin-binding module

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DESCRIPTION (provided by applicant): One of the ways we can understand how ubiquitin controls various processes is to define the protein interaction modules that can non-covalently bind ubiquitin. Finding such modules within proteins that are already implicated in ubiquitin-dependent processes can uncover new aspects for how these proteins function at the molecular level. Furthermore, finding such modules in other proteins can implicate a role for ubiquitin in processes where it was previously not suspected. We have found that a subset of WD40 beta propellers can bind Ub non covalently. This has led us to hypothesize that many WD40 beta propellers might bind ubiquitin and thus provide new dimension of ubiquitin-dependent control to a variety of biological processes. This proposal will set out to discovery new beta-propellers that bind Ub and discover the structural basis for this interaction. PUBLIC HEALTH RELEVANCE This proposal seeks new knowledge on how ubiquitin might control a wide variety of cellular processes. The work centers on discovering how ubiquitin non- covalently binds to WD40 beta propellers, which are found in many proteins with diverse functions. WD40 beta propeller proteins are involved in aspects of metabolism, diabetes, inflammation, immunology, aging, and neurobiology. This work promises mechanistic insight into how ubiquitin might regulate normal and pathogenic processes, which are of particular interest to many NIH institutes.