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PDBsum entry 4uu6
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Structural protein
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PDB id
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4uu6
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References listed in PDB file
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Key reference
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Title
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Structures of the human pals1 pdz domain with and without ligand suggest gated access of crb to the pdz peptide-Binding groove.
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Authors
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M.E.Ivanova,
G.C.Fletcher,
N.O'Reilly,
A.G.Purkiss,
B.J.Thompson,
N.Q.Mcdonald.
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Ref.
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Acta Crystallogr D Biol Crystallogr, 2015,
71,
555-564.
[DOI no: ]
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PubMed id
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Abstract
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Many components of epithelial polarity protein complexes possess PDZ domains
that are required for protein interaction and recruitment to the apical plasma
membrane. Apical localization of the Crumbs (Crb) transmembrane protein requires
a PDZ-mediated interaction with Pals1 (protein-associated with Lin7, Stardust,
MPP5), a member of the p55 family of membrane-associated guanylate kinases
(MAGUKs). This study describes the molecular interaction between the Crb
carboxy-terminal motif (ERLI), which is required for Drosophila cell polarity,
and the Pals1 PDZ domain using crystallography and fluorescence polarization.
Only the last four Crb residues contribute to Pals1 PDZ-domain binding affinity,
with specificity contributed by conserved charged interactions. Comparison of
the Crb-bound Pals1 PDZ structure with an apo Pals1 structure reveals a key Phe
side chain that gates access to the PDZ peptide-binding groove. Removal of this
side chain enhances the binding affinity by more than fivefold, suggesting that
access of Crb to Pals1 may be regulated by intradomain contacts or by
protein-protein interaction.
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