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|Title:||Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin||Authors:||Mukherjee, Manjeet
Chow, Soah Yee
Koh, Xiao Woon
Asgar, Nur Farehan M.
Jackson, Rebecca A.
Lim, Yoon Pin
Sze, Siu Kwan
Guy, Graeme R.
|Keywords:||DRNTU::Science::Biological sciences||Issue Date:||2012||Source:||Mukherjee, M., Chow, S. Y., Yusoff, P., Seetharaman, J., Ng, C., Sinniah, S., Koh, X. W., Asgar, N. F. M., 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. (2012). Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin. The EMBO Journal, 31(5), 1308-1319.||Series/Report no.:||The EMBO journal||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.||URI:||https://hdl.handle.net/10356/98086
|DOI:||10.1038/emboj.2011.496||Fulltext Permission:||none||Fulltext Availability:||No Fulltext|
|Appears in Collections:||SBS Journal Articles|
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