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PDBsum entry 3vk6
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References listed in PDB file
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Key reference
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Title
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Structure of a novel phosphotyrosine-Binding domain in hakai that targets e-Cadherin.
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Authors
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M.Mukherjee,
S.Y.Chow,
P.Yusoff,
J.Seetharaman,
C.Ng,
S.Sinniah,
X.W.Koh,
N.F.Asgar,
D.Li,
D.Yim,
R.A.Jackson,
J.Yew,
J.Qian,
A.Iyu,
Y.P.Lim,
X.Zhou,
S.K.Sze,
G.R.Guy,
J.Sivaraman.
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Ref.
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Embo J, 2012,
31,
1308-1319.
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PubMed id
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Abstract
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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.
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