8A5L
TRIM7 PRYSPRY in complex with a 2BC peptide TIEALFQ
Summary for 8A5L
| Entry DOI | 10.2210/pdb8a5l/pdb |
| Related | 7OVX 7OW2 |
| Descriptor | E3 ubiquitin-protein ligase TRIM7, 2BC peptide TIEALFQ, D(-)-TARTARIC ACID, ... (4 entities in total) |
| Functional Keywords | e3 ligase, pryspry, trim, protein binding |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 21306.07 |
| Authors | Luptak, J. (deposition date: 2022-06-15, release date: 2022-07-06, Last modification date: 2024-01-31) |
| Primary citation | 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 Cited by 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: 35893676DOI: 10.3390/v14081610 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.622 Å) |
Structure validation
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