The Francis Crick Institute
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A ubiquitin-binding domain that binds a structural fold distinct from that of ubiquitin.

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journal contribution
posted on 2020-01-09, 11:44 authored by Michael Lim, Joseph A Newman, Hannah L Williams, Laura Masino, Hazel Aitkenhead, Angeline E Gravard, Opher Gileadi, Jesper Q Svejstrup
Ubiquitylation, the posttranslational 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 by mediating interactions with ubiquitylated proteins. The chromatin remodeler, SMARCAD1, interacts with KAP1, a transcriptional corepressor. The SMARCAD1-KAP1 interaction is direct and involves the first SMARCAD1 CUE domain (CUE1) and the RBCC domain of KAP1. Here, we present a structural model of the KAP1 RBCC-SMARCAD1 CUE1 complex based on X-ray crystallography. Remarkably, CUE1, a canonical CUE domain, recognizes a cluster of exposed hydrophobic and surrounding charged/amphipathic residues on KAP1, which are presented in the context of a coiled-coil domain, not in a structure resembling ubiquitin. Together, these data suggest that CUE domains may have a wider function than simply recognizing ubiquitin and the ubiquitin-fold.


Crick (Grant ID: 10166, Grant title: Svejstrup FC001166) European Research Council (Grant ID: 693327 - TRANSDAM, Grant title: ERC 693327 - TRANSDAM)