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Structure of SIL1-bound FEM1CStructure of SIL1-bound FEM1C
Structural highlights
DiseaseSIL1_HUMAN Marinesco-Sjoegren syndrome. The disease is caused by variants affecting the gene represented in this entry. FunctionFEM1C_HUMAN Probable component of an E3 ubiquitin-protein ligase complex, in which it may act as a substrate recognition subunit.SIL1_HUMAN Required for protein translocation and folding in the endoplasmic reticulum (ER). Functions as a nucleotide exchange factor for the ER lumenal chaperone HSPA5.[1] Publication Abstract from PubMedDegrons are elements within protein substrates that mediate the interaction with specific degradation machineries to control proteolysis. Recently, a few classes of C-terminal degrons (C-degrons) that are recognized by dedicated cullin-RING ligases (CRLs) have been identified. Specifically, CRL2 using the related substrate adapters FEM1A/B/C was found to recognize C degrons ending with arginine (Arg/C-degron). Here, we uncover the molecular mechanism of Arg/C-degron recognition by solving a subset of structures of FEM1 proteins in complex with Arg/C-degron-bearing substrates. Our structural research, complemented by binding assays and global protein stability (GPS) analyses, demonstrates that FEM1A/C and FEM1B selectively target distinct classes of Arg/C-degrons. Overall, our study not only sheds light on the molecular mechanism underlying Arg/C-degron recognition for precise control of substrate turnover, but also provides valuable information for development of chemical probes for selectively regulating proteostasis. Molecular basis for arginine C-terminal degron recognition by Cul2(FEM1) E3 ligase.,Chen X, Liao S, Makaros Y, Guo Q, Zhu Z, Krizelman R, Dahan K, Tu X, Yao X, Koren I, Xu C Nat Chem Biol. 2021 Jan 4. pii: 10.1038/s41589-020-00704-3. doi:, 10.1038/s41589-020-00704-3. PMID:33398168[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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