8A5M

TRIM7 PRYSPRY in complex with a MNV1-NS6 peptide LEALEFQ

8A5M の概要

• エントリーDOI: 10.2210/pdb8a5m/pdb
• 関連するPDBエントリー: 7OVX 7OW2 8A5L
• 分子名称: E3 ubiquitin-protein ligase TRIM7, MNV1-NS6 peptide LEALEFQ, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: e3 ligase, pryspry, trim, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 42652.90

構造登録者

Luptak, J. (登録日: 2022-06-15, 公開日: 2022-07-06, 最終更新日: 2024-01-31)

主引用文献

Luptak, J.,Mallery, D.L.,Jahun, A.S.,Albecka, A.,Clift, D.,Ather, O.,Slodkowicz, G.,Goodfellow, I.,James, L.C.
TRIM7 Restricts Coxsackievirus and Norovirus Infection by Detecting the C-Terminal Glutamine Generated by 3C Protease Processing.
Viruses, 14:-, 2022

PubMed Abstract: 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-ΦQ' 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.

PubMed: 35893676
DOI: 10.3390/v14081610

実験手法

X-RAY DIFFRACTION (2.918 Å)