A Ubiquitin-Binding Domain that Binds a Structural Fold Distinct from that of Ubiquitin.

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.