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PDBsum entry 4wsi
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Peptide binding protein
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PDB id
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4wsi
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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 crumbs tail in complex with the pals1 pdz-Sh3-Gk tandem reveals a highly specific assembly mechanism for the apical crumbs complex.
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Authors
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Y.Li,
Z.Wei,
Y.Yan,
Q.Wan,
Q.Du,
M.Zhang.
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Ref.
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Proc Natl Acad Sci U S A, 2014,
111,
17444-17449.
[DOI no: ]
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PubMed id
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Abstract
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The Crumbs (Crb) complex, formed by Crb, PALS1, and PATJ, is evolutionarily
conserved in metazoans and acts as a master cell-growth and -polarity regulator
at the apical membranes in polarized epithelia. Crb intracellular functions,
including its direct binding to PALS1, are mediated by Crb's highly conserved
37-residue cytoplasmic tail. However, the mechanistic basis governing the highly
specific Crb-PALS1 complex formation is unclear, as reported interaction between
the Crb tail (Crb-CT) and PALS1 PSD-95/DLG/ZO-1 (PDZ) domain is weak and
promiscuous. Here we have discovered that the PDZ-Src homolgy 3 (SH3)-Guanylate
kinase (GK) tandem of PALS1 binds to Crb-CT with a dissociation constant of 70
nM, which is ∼100-fold stronger than the PALS1 PDZ-Crb-CT interaction. The
crystal structure of the PALS1 PDZ-SH3-GK-Crb-CT complex reveals that PDZ-SH3-GK
forms a structural supramodule with all three domains contributing to the tight
binding to Crb. Mutations disrupting the tertiary interactions of the PDZ-SH3-GK
supramodule weaken the PALS1-Crb interaction and compromise PALS1-mediated
polarity establishment in Madin-Darby canine kidney (MDCK) cysts. We further
show that specific target binding of other members of membrane-associated
guanylate kinases (MAGUKs) (e.g., CASK binding to neurexin) also requires the
presence of their PDZ-SH3-GK tandems.
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