7yc2

Structural highlights

Function

ZY11B_HUMAN Serves as substrate adapter subunit in the E3 ubiquitin ligase complex ZYG11B-CUL2-Elongin BC. Acts to target substrates bearing N-terminal degrons for proteasomal degradation with the first four residues of substrates being the key recognition elements (PubMed:33093214, PubMed:34214466, PubMed:35636250). Prefers Nt-Gly but also has the capacity to recognize Nt-Ser, -Ala and -Cys (PubMed:36496439). Involved in the clearance of proteolytic fragments generated by caspase cleavage during apoptosis since N-terminal glycine degrons are strongly enriched at caspase cleavage sites. Also important in the quality control of protein N-myristoylation in which N-terminal glycine degrons are conditionally exposed after a failure of N-myristoylation (PubMed:31273098). In addition, plays a role in the amplification of cGAS to enhance innate immune response. Mechanistically, strengthens the processes of cGAS binding with dsDNA and assembling oligomers and also accelerates and stabilizes cGAS-DNA condensation, thereby enhancing production of antiviral IFNs and inflammatory cytokines (PubMed:36933219).^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Timms RT, Zhang Z, Rhee DY, Harper JW, Koren I, Elledge SJ. A glycine-specific N-degron pathway mediates the quality control of protein N-myristoylation. Science. 2019 Jul 5;365(6448):eaaw4912. doi: 10.1126/science.aaw4912. PMID:31273098 doi:http://dx.doi.org/10.1126/science.aaw4912
2. ↑ Robinson KS, Teo DET, Tan KS, Toh GA, Ong HH, Lim CK, Lay K, Au BV, Lew TS, Chu JJH, Chow VTK, Wang Y, Zhong FL, Reversade B. Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia. Science. 2020 Dec 4;370(6521):eaay2002. doi: 10.1126/science.aay2002. Epub 2020 , Oct 22. PMID:33093214 doi:http://dx.doi.org/10.1126/science.aay2002
3. ↑ Yan X, Li Y, Wang G, Zhou Z, Song G, Feng Q, Zhao Y, Mi W, Ma Z, Dong C. Molecular basis for recognition of Gly/N-degrons by CRL2(ZYG11B) and CRL2(ZER1). Mol Cell. 2021 Aug 19;81(16):3262-3274.e3. PMID:34214466 doi:10.1016/j.molcel.2021.06.010
4. ↑ Zhang B, Li Y, Feng Q, Song L, Dong C, Yan X. Structural insights into ORF10 recognition by ZYG11B. Biochem Biophys Res Commun. 2022 Aug 6;616:14-18. PMID:35636250 doi:10.1016/j.bbrc.2022.05.069
5. ↑ Li Y, Zhao Y, Yan X, Ye C, Weirich S, Zhang B, Wang X, Song L, Jiang C, Jeltsch A, Dong C, Mi W. CRL2(ZER1/ZYG11B) recognizes small N-terminal residues for degradation. Nat Commun. 2022 Dec 10;13(1):7636. doi: 10.1038/s41467-022-35169-6. PMID:36496439 doi:http://dx.doi.org/10.1038/s41467-022-35169-6
6. ↑ Zhang J, Zhou EC, He Y, Chai ZL, Ji BZ, Tu Y, Wang HL, Wu WQ, Liu Y, Zhang XH, Liu Y. ZYG11B potentiates the antiviral innate immune response by enhancing cGAS-DNA binding and condensation. Cell Rep. 2023 Mar 28;42(3):112278. PMID:36933219 doi:10.1016/j.celrep.2023.112278