3VK6

Crystal structure of a phosphotyrosine binding domain

Summary for 3VK6

• Entry DOI: 10.2210/pdb3vk6/pdb
• Descriptor: E3 ubiquitin-protein ligase Hakai, ZINC ION (3 entities in total)
• Functional Keywords: hyb, phosphotyrosine binding domain, ligase
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 1
• Total formula weight: 11750.90

Authors

Sivaraman, J.,Mukherjee, M. (deposition date: 2011-11-09, release date: 2012-01-25, Last modification date: 2024-03-20)

Primary citation

Mukherjee, M.,Chow, S.Y.,Yusoff, P.,Seetharaman, J.,Ng, C.,Sinniah, S.,Koh, X.W.,Asgar, N.F.,Li, D.,Yim, D.,Jackson, R.A.,Yew, J.,Qian, J.,Iyu, A.,Lim, Y.P.,Zhou, X.,Sze, S.K.,Guy, G.R.,Sivaraman, J.
Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin
Embo J., 31:1308-1319, 2012

PubMed Abstract: Phosphotyrosine-binding domains, typified by the SH2 (Src homology 2) and PTB domains, are critical upstream components of signal transduction pathways. The E3 ubiquitin ligase Hakai targets tyrosine-phosphorylated E-cadherin via an uncharacterized domain. In this study, the crystal structure of Hakai (amino acids 106-206) revealed that it forms an atypical, zinc-coordinated homodimer by utilizing residues from the phosphotyrosine-binding domain of two Hakai monomers. Hakai dimerization allows the formation of a phosphotyrosine-binding pocket that recognizes specific phosphorylated tyrosines and flanking acidic amino acids of Src substrates, such as E-cadherin, cortactin and DOK1. NMR and mutational analysis identified the Hakai residues required for target binding within the binding pocket, now named the HYB domain. ZNF645 also possesses a HYB domain but demonstrates different target specificities. The HYB domain is structurally different from other phosphotyrosine-binding domains and is a potential drug target due to its novel structural features.

PubMed: 22252131
DOI: 10.1038/emboj.2011.496

Experimental method

X-RAY DIFFRACTION (1.9 Å)