7y3b

Crystal structure of TRIM7 bound to GN1Crystal structure of TRIM7 bound to GN1

Structural highlights

7y3b is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.76Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TRIM7_HUMAN E3 ubiquitin-protein ligase. Mediates 'Lys-63'-linked polyubiquitination and stabilization of the JUN coactivator RNF187 in response to growth factor signaling via the MEK/ERK pathway, thereby regulating JUN transactivation and cellular proliferation (PubMed:25851810). Promotes the TLR4-mediated signaling activation through its E3 ligase domain leading to production of proinflammatory cytokines and type I interferon (By similarity). Plays also a negative role in the regulation of exogenous cytosolic DNA virus-triggered immune response. Mechanistically, enhances the 'Lys-48'-linked ubiquitination of STING1 leading to its proteasome-dependent degradation (PubMed:32126128).[UniProtKB:Q923T7]^[1] ^[2] (Microbial infection) Promotes Zika virus replication by mediating envelope protein E ubiquitination.^[3]

Publication Abstract from PubMed

The exposed N-terminal or C-terminal residues of proteins can act, in cognate sequence contexts, as degradation signals (degrons) that are targeted by specific E3 ubiquitin ligases for proteasome-dependent degradation by N-degron or C-degron pathways. Here, we discovered a distinct C-degron pathway, termed the Gln/C-degron pathway, in which the B30.2 domain of E3 ubiquitin ligase TRIM7 (TRIM7(B30.2)) mediates the recognition of proteins bearing a C-terminal glutamine. By determining crystal structures of TRIM7(B30.2) in complexes with various peptides, we show that TRIM7(B30.2) forms a positively charged binding pocket to engage the "U"-shaped Gln/C-degron. The four C-terminal residues of a substrate play an important role in C-degron recognition, with C-terminal glutamine as the principal determinant. In vitro biochemical and cellular experiments were used to further analyze the substrate specificity and selective degradation of the Gln/C-degron by TRIM7.

C-terminal glutamine acts as a C-degron targeted by E3 ubiquitin ligase TRIM7.,Ru Y, Yan X, Zhang B, Song L, Feng Q, Ye C, Zhou Z, Yang Z, Li Y, Zhang Z, Li Q, Mi W, Dong C Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2203218119. doi:, 10.1073/pnas.2203218119. Epub 2022 Jul 22. PMID:35867826^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chakraborty A, Diefenbacher ME, Mylona A, Kassel O, Behrens A. The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling. Nat Commun. 2015 Apr 8;6:6782. doi: 10.1038/ncomms7782. PMID:25851810 doi:http://dx.doi.org/10.1038/ncomms7782
↑ Yang B, Liu Y, Cui Y, Song D, Zhang G, Ma S, Liu Y, Chen M, Chen F, Wang H, Wang J. RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation. PLoS Pathog. 2020 Mar 3;16(3):e1008387. doi: 10.1371/journal.ppat.1008387., eCollection 2020 Mar. PMID:32126128 doi:http://dx.doi.org/10.1371/journal.ppat.1008387
↑ Giraldo MI, Xia H, Aguilera-Aguirre L, Hage A, van Tol S, Shan C, Xie X, Sturdevant GL, Robertson SJ, McNally KL, Meade-White K, Azar SR, Rossi SL, Maury W, Woodson M, Ramage H, Johnson JR, Krogan NJ, Morais MC, Best SM, Shi PY, Rajsbaum R. Envelope protein ubiquitination drives entry and pathogenesis of Zika virus. Nature. 2020 Sep;585(7825):414-419. doi: 10.1038/s41586-020-2457-8. Epub 2020 Jul, 8. PMID:32641828 doi:http://dx.doi.org/10.1038/s41586-020-2457-8
↑ Ru Y, Yan X, Zhang B, Song L, Feng Q, Ye C, Zhou Z, Yang Z, Li Y, Zhang Z, Li Q, Mi W, Dong C. C-terminal glutamine acts as a C-degron targeted by E3 ubiquitin ligase TRIM7. Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2203218119. doi:, 10.1073/pnas.2203218119. Epub 2022 Jul 22. PMID:35867826 doi:http://dx.doi.org/10.1073/pnas.2203218119

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OCA

[1] Chakraborty A, Diefenbacher ME, Mylona A, Kassel O, Behrens A. The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling. Nat Commun. 2015 Apr 8;6:6782. doi: 10.1038/ncomms7782. PMID:25851810 doi:http://dx.doi.org/10.1038/ncomms7782

[2] Yang B, Liu Y, Cui Y, Song D, Zhang G, Ma S, Liu Y, Chen M, Chen F, Wang H, Wang J. RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation. PLoS Pathog. 2020 Mar 3;16(3):e1008387. doi: 10.1371/journal.ppat.1008387., eCollection 2020 Mar. PMID:32126128 doi:http://dx.doi.org/10.1371/journal.ppat.1008387

[3] Giraldo MI, Xia H, Aguilera-Aguirre L, Hage A, van Tol S, Shan C, Xie X, Sturdevant GL, Robertson SJ, McNally KL, Meade-White K, Azar SR, Rossi SL, Maury W, Woodson M, Ramage H, Johnson JR, Krogan NJ, Morais MC, Best SM, Shi PY, Rajsbaum R. Envelope protein ubiquitination drives entry and pathogenesis of Zika virus. Nature. 2020 Sep;585(7825):414-419. doi: 10.1038/s41586-020-2457-8. Epub 2020 Jul, 8. PMID:32641828 doi:http://dx.doi.org/10.1038/s41586-020-2457-8

[4] Ru Y, Yan X, Zhang B, Song L, Feng Q, Ye C, Zhou Z, Yang Z, Li Y, Zhang Z, Li Q, Mi W, Dong C. C-terminal glutamine acts as a C-degron targeted by E3 ubiquitin ligase TRIM7. Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2203218119. doi:, 10.1073/pnas.2203218119. Epub 2022 Jul 22. PMID:35867826 doi:http://dx.doi.org/10.1073/pnas.2203218119

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