4WQO

Structure of VHL-EloB-EloC-Cul2

Summary for 4WQO

• Entry DOI: 10.2210/pdb4wqo/pdb
• Descriptor: Von Hippel-Lindau disease tumor suppressor, Transcription elongation factor B polypeptide 2, Transcription elongation factor B polypeptide 1, ... (4 entities in total)
• Functional Keywords: e3 ligase complex, transcription
• Biological source: Homo sapiens (Human); More
• Cellular location: Isoform 1: Cytoplasm. Isoform 3: Cytoplasm: P40337; Nucleus : Q15370 Q15369
• Total number of polymer chains: 4
• Total formula weight: 72474.79

Authors

Nguyen, H.C.,Xiong, Y. (deposition date: 2014-10-22, release date: 2015-03-04, Last modification date: 2023-09-27)

Primary citation

Nguyen, H.C.,Yang, H.,Fribourgh, J.L.,Wolfe, L.S.,Xiong, Y.
Insights into Cullin-RING E3 Ubiquitin Ligase Recruitment: Structure of the VHL-EloBC-Cul2 Complex.
Structure, 23:441-449, 2015

PubMed 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.

PubMed: 25661653
DOI: 10.1016/j.str.2014.12.014

Experimental method

X-RAY DIFFRACTION (3.2 Å)