Other
19 Authors
- Mukherjee M,
- Qian J,
- Yusoff P,
- Yim D,
- Koh XW,
- Seetharaman J,
- Yew J,
- Jackson RA,
- Sze SK,
- Zhou X,
- Ng C,
- Chow SY,
- Li D,
- Iyu A,
- Asgar NF,
- Sinniah S,
- Guy GR,
- Lim YP,
- Sivaraman J
| First Author | Mukherjee M | Year | 2012 |
| Journal | EMBO J | Volume | 31 |
| Issue | 5 | Pages | 1308-19 |
| PubMed ID | 22252131 | Mgi Jnum | J:200486 |
| Mgi Id | MGI:5508715 | Doi | 10.1038/emboj.2011.496 |
| Citation | Mukherjee M, et al. (2012) Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin. EMBO J 31(5):1308-19 |
| abstractText | 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. |
