+Search query
-Structure paper
| Title | Structural basis for L-isoaspartyl-containing protein recognition by the human PCMTD1 cullin-RING E3 ubiquitin ligase. |
|---|---|
| Journal, issue, pages | J Biol Chem, Vol. 301, Issue 11, Page 110735, Year 2025 |
| Publish date | Sep 18, 2025 |
Authors | Eric Z Pang / Boyu Zhao / Cameron Flowers / Elizabeth Oroudjeva / Jasmine B Winter / Vijaya Pandey / Michael R Sawaya / James Wohlschlegel / Joseph A Loo / Jose A Rodriguez / Steven G Clarke / ![]() |
| PubMed Abstract | A major type of spontaneous protein damage that accumulates with age is the formation of kinked polypeptide chains with L-isoaspartyl residues. Mitigating this damage is necessary for maintaining ...A major type of spontaneous protein damage that accumulates with age is the formation of kinked polypeptide chains with L-isoaspartyl residues. Mitigating this damage is necessary for maintaining proteome stability and prolonging organismal survival. Although repair through methylation by PCMT1 has been previously shown to suppress L-isoaspartyl accumulation, we provide an additional mechanism for L-isoaspartyl maintenance through PCMTD1, a cullin-RING ligase (CRL). We combined cryo-EM, native mass spectrometry, and biochemical assays to provide insight on how the assembly and architecture of human PCMTD1 in the context of a CRL complex fulfills this alternative mechanism. We show that the PCMTD1 CRL complex specifically binds L-isoaspartyl residues when bound to AdoMet. This work provides evidence for a growing class of E3 ubiquitin ligases that recognizes spontaneous covalent modifications as potential substrates for ubiquitylation and subsequent proteasomal degradation. |
External links | J Biol Chem / PubMed:40975169 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 4.14 - 9.72 Å |
| Structure data | EMDB-70610, PDB-9oma: EMDB-70612, PDB-9omf: |
| Source |
|
Keywords | PROTEIN BINDING / CUL5-RING ubiquitin ligase complex |
Movie
Controller
Structure viewers
About Yorodumi Papers



Authors
External links



homo sapiens (human)
Keywords