8a8x

From Proteopedia

Jump to: navigation, search

TRIM7 PRYSPRY in complex with a MNV1-NS3 peptide HDDFGLQ

Structural highlights

8a8x is a 4 chain structure with sequence from Homo sapiens and Murine norovirus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.37Å
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

TRIM7 catalyzes the ubiquitination of multiple substrates with unrelated biological functions. This cross-reactivity is at odds with the specificity usually displayed by enzymes, including ubiquitin ligases. Here we show that TRIM7's extreme substrate promiscuity is due to a highly unusual binding mechanism, in which the PRYSPRY domain captures any ligand with a C-terminal helix that terminates in a hydrophobic residue followed by a glutamine. Many of the non-structural proteins found in RNA viruses contain C-terminal glutamines as a result of polyprotein cleavage by 3C protease. This viral processing strategy generates novel substrates for TRIM7 and explains its ability to inhibit Coxsackie virus and norovirus replication. In addition to viral proteins, cellular proteins such as glycogenin have evolved C-termini that make them a TRIM7 substrate. The 'helix-PhiQ' degron motif recognized by TRIM7 is reminiscent of the N-end degron system and is found in ~1% of cellular proteins. These features, together with TRIM7's restricted tissue expression and lack of immune regulation, suggest that viral restriction may not be its physiological function.

TRIM7 Restricts Coxsackievirus and Norovirus Infection by Detecting the C-Terminal Glutamine Generated by 3C Protease Processing.,Luptak J, Mallery DL, Jahun AS, Albecka A, Clift D, Ather O, Slodkowicz G, Goodfellow I, James LC Viruses. 2022 Jul 23;14(8). pii: v14081610. doi: 10.3390/v14081610. PMID:35893676[4]

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

Loading citation details..
Citations
1 reviews cite this structure
Interplay between TRIM7 and antiviral immunity.
Liu et al. (2023)
0 more
1 other articles
No citations found

References

  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. ↑ Luptak J, Mallery DL, Jahun AS, Albecka A, Clift D, Ather O, Slodkowicz G, Goodfellow I, James LC. TRIM7 Restricts Coxsackievirus and Norovirus Infection by Detecting the C-Terminal Glutamine Generated by 3C Protease Processing. Viruses. 2022 Jul 23;14(8). pii: v14081610. doi: 10.3390/v14081610. PMID:35893676 doi:http://dx.doi.org/10.3390/v14081610

Contents


PDB ID 8a8x

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://proteopedia.org/wiki/index.php/8a8x"
Personal tools