7YNX

Crystal structure of Pirh2 bound to poly-Ala peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.220 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

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.

(2023) Nat Commun 14: 2474-2474

  • DOI: https://doi.org/10.1038/s41467-023-38173-6
  • Primary Citation of Related Structures:  
    7YNX

  • 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.


  • Organizational Affiliation

    The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Haihe Laboratory of Cell Ecosystem, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RING finger and CHY zinc finger domain-containing protein 1
A, B
203Homo sapiensMutation(s): 0 
Gene Names: RCHY1ARNIPCHIMPPIRH2RNF199ZNF363
EC: 2.3.2.27
UniProt & NIH Common Fund Data Resources
Find proteins for Q96PM5 (Homo sapiens)
Explore Q96PM5 
Go to UniProtKB:  Q96PM5
PHAROS:  Q96PM5
GTEx:  ENSG00000163743 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ96PM5
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
BA [auth B],
CA [auth B],
DA [auth B],
K [auth A],
L [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
ZN (Subject of Investigation/LOI)
Query on ZN

Download Ideal Coordinates CCD File 
AA [auth B]
C [auth A]
D [auth A]
E [auth A]
F [auth A]
AA [auth B],
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
T [auth B],
U [auth B],
V [auth B],
W [auth B],
X [auth B],
Y [auth B],
Z [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
NA
Query on NA

Download Ideal Coordinates CCD File 
EA [auth B]
FA [auth B]
GA [auth B]
HA [auth B]
IA [auth B]
EA [auth B],
FA [auth B],
GA [auth B],
HA [auth B],
IA [auth B],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A],
R [auth A],
S [auth A]
SODIUM ION
Na
FKNQFGJONOIPTF-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.220 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.47α = 90
b = 80.27β = 90
c = 84.87γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
XDSdata reduction
XDSdata scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of China (NSFC)China31900865
National Natural Science Foundation of China (NSFC)China32071193
National Natural Science Foundation of China (NSFC)China81874039

Revision History  (Full details and data files)

  • Version 1.0: 2023-04-26
    Type: Initial release
  • Version 1.1: 2023-05-17
    Changes: Database references, Structure summary
  • Version 1.2: 2024-05-29
    Changes: Data collection