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PDBsum entry 5o2q
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Structure from cyana 3.97
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PDB id
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5o2q
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References listed in PDB file
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Key reference
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Title
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Structural characterization of cas sh3 domain selectivity and regulation reveals new cas interaction partners.
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Authors
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J.Gemperle,
R.Hexnerová,
M.Lepšík,
P.Tesina,
M.Dibus,
M.Novotný,
J.Brábek,
V.Veverka,
D.Rosel.
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Ref.
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Sci Rep, 2017,
7,
8057.
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PubMed id
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Abstract
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CAS is a docking protein downstream of the proto-oncogene Src with a role in
invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for
CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and
regulation are not well understood. Here, we identified the consensus CAS SH3
binding motif and structurally characterized the CAS SH3 domain in complex with
ligand. We revealed the requirement for an uncommon centrally localized lysine
residue at position +2 of CAS SH3 ligands and two rather dissimilar optional
anchoring residues, leucine and arginine, at position +5. We further expanded
the knowledge of CAS SH3 ligand binding regulation by manipulating tyrosine 12
phosphorylation and confirmed the negative role of this phosphorylation on CAS
SH3 ligand binding. Finally, by exploiting the newly identified binding
requirements of the CAS SH3 domain, we predicted and experimentally verified two
novel CAS SH3 binding partners, DOK7 and GLIS2.
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