7YNX

Crystal structure of Pirh2 bound to poly-Ala peptide

Summary for 7YNX

• Entry DOI: 10.2210/pdb7ynx/pdb
• Descriptor: RING finger and CHY zinc finger domain-containing protein 1, ZINC ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: e3 ligase, ligase, cytosolic protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 47639.42

Authors

Dong, C.,Yan, X.,Li, Y. (deposition date: 2022-08-01, release date: 2023-04-26, Last modification date: 2024-05-29)

Primary citation

Wang, X.,Li, Y.,Yan, X.,Yang, Q.,Zhang, B.,Zhang, Y.,Yuan, X.,Jiang, C.,Chen, D.,Liu, Q.,Liu, T.,Mi, W.,Yu, Y.,Dong, C.
Recognition of an Ala-rich C-degron by the E3 ligase Pirh2.
Nat Commun, 14:2474-2474, 2023

PubMed Abstract: The ribosome-associated quality-control (RQC) pathway degrades aberrant nascent polypeptides arising from ribosome stalling during translation. In mammals, the E3 ligase Pirh2 mediates the degradation of aberrant nascent polypeptides by targeting the C-terminal polyalanine degrons (polyAla/C-degrons). Here, we present the crystal structure of Pirh2 bound to the polyAla/C-degron, which shows that the N-terminal domain and the RING domain of Pirh2 form a narrow groove encapsulating the alanine residues of the polyAla/C-degron. Affinity measurements in vitro and global protein stability assays in cells further demonstrate that Pirh2 recognizes a C-terminal A/S-X-A-A motif for substrate degradation. Taken together, our study provides the molecular basis underlying polyAla/C-degron recognition by Pirh2 and expands the substrate recognition spectrum of Pirh2.

PubMed: 37120596
DOI: 10.1038/s41467-023-38173-6

Experimental method

X-RAY DIFFRACTION (2.3 Å)