Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/98086
Title: Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin
Authors: Mukherjee, Manjeet
Chow, Soah Yee
Yusoff, Permeen
Seetharaman, J.
Ng, Cherlyn
Sinniah, Saravanan
Koh, Xiao Woon
Asgar, Nur Farehan M.
Li, Dan
Yim, Daniel
Jackson, Rebecca A.
Yew, Jingxi
Qian, Jingru
Iyu, Audrey
Lim, Yoon Pin
Zhou, Xingding
Sze, Siu Kwan
Guy, Graeme R.
Sivaraman, J.
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
http://hdl.handle.net/10220/13290
DOI: 10.1038/emboj.2011.496
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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