Abstract:
:Proteome integrity depends on the ubiquitin-proteasome system to degrade unwanted or abnormal proteins. In addition to the N-degrons, C-terminal residues of proteins can also serve as degradation signals (C-degrons) that are recognized by specific cullin-RING ubiquitin ligases (CRLs) for proteasomal degradation. FEM1C is a CRL2 substrate receptor that targets the C-terminal arginine degron (Arg/C-degron), but the molecular mechanism of substrate recognition remains largely elusive. Here, we present crystal structures of FEM1C in complex with Arg/C-degron and show that FEM1C utilizes a semi-open binding pocket to capture the C-terminal arginine and that the extreme C-terminal arginine is the major structural determinant in recognition by FEM1C. Together with biochemical and mutagenesis studies, we provide a framework for understanding molecular recognition of the Arg/C-degron by the FEM family of proteins.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Yan X,Wang X,Li Y,Zhou M,Li Y,Song L,Mi W,Min J,Dong Cdoi
10.1038/s41589-020-00703-4subject
Has Abstractpub_date
2021-01-04 00:00:00eissn
1552-4450issn
1552-4469pii
10.1038/s41589-020-00703-4pub_type
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