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VHL Domain
Structure:

No ImageThe beta-domain of the von Hippel-Lindau tumor suppressor protein (VHL) is composed of a seven-stranded beta sandwich, located at the amino-terminus, and a carboxy-terminal alpha helix which is held against one of the beta strands through hydrophobic interactions. The beta sandwich forms a partially exposed hydrophobic core which, along with other polar residues, provides the binding site for the hydroxyproline peptide-containing ligand. This interaction is mediated by multiple van der Waals contacts between Trp88, Tyr98, and Trp117 of VHL to the pyrrolidine ring and hydrogen bonds between His115 to the 4-hydroxyl group of the hydroxyproline.
 

Structure Reference:
Min, J. et al., (2002) Science. 296(5574): 1886-1889.
The VHL domain bound to a hydroxylproline peptide of HIFα.
PDB: 1LM8.

Domain binding and function:
VHL complexes with ElonginC, ElonginB, Cul2, and Rbx1 to form an E3 ubiquitin-protein ligase in which VHL acts as the substrate recognition subunit. The beta domain of VHL is approximately 100 amino acids and has been shown to interact with hydroxylated prolines within target proteins. Contact residues in the beta domain of VHL are well conserved in human, fly, frog and worm VHL orthologs. Substrates are subsequently polyubiquitinated and targeted for proteasomal degradation. The VHL beta domain has been shown to interact with specific hydroxylated prolines of HIF-1α and the large subunit of RNA polymerase II. The VHL beta domain has also been shown to interact with several atypical PKC isotypes.
Examples of Proteins: 
Hydroxyproline-containing proteins
HIF-1α
RNA Polymerase II
Other proteins
Atypical PKC isotypes

 
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