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7ynx
From Proteopedia
Crystal structure of Pirh2 bound to poly-Ala peptide
Structural highlights
FunctionZN363_HUMAN Mediates E3-dependent ubiquitination and proteasomal degradation of target proteins, including p53/TP53, P73, HDAC1 and CDKN1B. Preferentially acts on tetrameric p53/TP53. Monoubiquitinates the translesion DNA polymerase POLH. Contributes to the regulation of the cell cycle progression. Increases AR transcription factor activity.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe 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. Recognition of an Ala-rich C-degron by the E3 ligase Pirh2.,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 Nat Commun. 2023 Apr 29;14(1):2474. doi: 10.1038/s41467-023-38173-6. PMID:37120596[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Dong C | Li Y | Yan X
