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bioRxiv · 10.1101/375832

A Ubiquitin-Binding Domain that Does Not Bind Ubiquitin

Lim, M.·Newman, J. A.·Williams, H. L.·Aitkenhead, H.·Gileadi, O.·Svejstrup, J.
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Abstract

Ubiquitylation, the post-translational linkage of ubiquitin moieties to lysines in target proteins, helps regulate a myriad of biological processes. Ubiquitin, and sometimes ubiquitin-homology domains, are recognized by ubiquitin-binding domains, including CUE domains. CUE domains are thus generally thought to function exclusively by mediating interactions with ubiquitylated proteins. The chromatin remodeler, SMARCAD1, interacts with KAP1, a transcriptional corepressor. We show that the SMARCAD1-KAP1 interaction is direct and involves the first SMARCAD1 CUE domain (CUE1) and the RBCC domain of KAP1. A structural model of the minimal KAP1 RBCC-SMARCAD1 CUE1 complex based on X-ray crystallography analysis is presented. Remarkably, the CUE1 domain, which resembles a canonical CUE domain, recognizes 2 clusters of exposed hydrophobic residues on KAP1, but these are presented in the context of a coiled-coil domain, not in a structure resembling ubiquitin. Together, these data challenge the well-established dogma that CUE domains exclusively recognize the ubiquitin-fold.

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Lim, M., Newman, J. A., Williams, H. L., Aitkenhead, H., Gileadi, O., Svejstrup, J.. 2018-07-24. A Ubiquitin-Binding Domain that Does Not Bind Ubiquitin. https://doi.org/10.1101/375832

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