PDBsum entry 4wqo

Transcription

PDB id: 4wqo

Contents

Protein chains

148 a.a.

104 a.a.

96 a.a.

141 a.a.

References listed in PDB file

Key reference

• Title: Insights into cullin-Ring e3 ubiquitin ligase recruitment: structure of the vhl-Elobc-Cul2 complex.
• Authors: H.C.Nguyen, H.Yang, J.L.Fribourgh, L.S.Wolfe, Y.Xiong.
• Ref.: Structure, 2015, 23, 441-449. [DOI no: 10.1016/j.str.2014.12.014]
• PubMed id: 25661653

Abstract

The von Hippel-Lindau tumor suppressor protein (VHL) recruits a Cullin 2 (Cul2) E3 ubiquitin ligase to downregulate HIF-1α, an essential transcription factor for the hypoxia response. Mutations in VHL lead to VHL disease and renal cell carcinomas. Inhibition of this pathway to upregulate erythropoietin production is a promising new therapy to treat ischemia and chronic anemia. Here, we report the crystal structure of VHL bound to a Cul2 N-terminal domain, Elongin B, and Elongin C (EloC). Cul2 interacts with both the VHL BC box and cullin box and a novel EloC site. Comparison with other cullin E3 ligase structures shows that there is a conserved, yet flexible, cullin recognition module and that cullin selectivity is influenced by distinct electrostatic interactions. Our structure provides a structural basis for the study of the pathogenesis of VHL disease and rationale for the design of novel compounds that may modulate cullin-substrate receptor interactions.