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PDBsum entry 3ifq
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Cell adhesion
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PDB id
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3ifq
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References listed in PDB file
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Key reference
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Title
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Interactions of plakoglobin and beta-Catenin with desmosomal cadherins: basis of selective exclusion of alpha- And beta-Catenin from desmosomes.
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Authors
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H.J.Choi,
J.C.Gross,
S.Pokutta,
W.I.Weis.
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Ref.
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J Biol Chem, 2009,
284,
31776-31788.
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PubMed id
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Abstract
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Plakoglobin and beta-catenin are homologous armadillo repeat proteins found in
adherens junctions, where they interact with the cytoplasmic domain of classical
cadherins and with alpha-catenin. Plakoglobin, but normally not beta-catenin, is
also a structural constituent of desmosomes, where it binds to the cytoplasmic
domains of the desmosomal cadherins, desmogleins and desmocollins. Here, we
report structural, biophysical, and biochemical studies aimed at understanding
the molecular basis of selective exclusion of beta-catenin and alpha-catenin
from desmosomes. The crystal structure of the plakoglobin armadillo domain bound
to phosphorylated E-cadherin shows virtually identical interactions to those
observed between beta-catenin and E-cadherin. Trypsin sensitivity experiments
indicate that the plakoglobin arm domain by itself is more flexible than that of
beta-catenin. Binding of plakoglobin and beta-catenin to the intracellular
regions of E-cadherin, desmoglein1, and desmocollin1 was measured by isothermal
titration calorimetry. Plakoglobin and beta-catenin bind strongly and with
similar thermodynamic parameters to E-cadherin. In contrast, beta-catenin binds
to desmoglein-1 more weakly than does plakoglobin. beta-Catenin and plakoglobin
bind with similar weak affinities to desmocollin-1. Full affinity binding of
desmoglein-1 requires sequences C-terminal to the region homologous to the
catenin-binding domain of classical cadherins. Although pulldown assays suggest
that the presence of N- and C-terminal beta-catenin "tails" that flank the
armadillo repeat region reduces the affinity for desmosomal cadherins,
calorimetric measurements show no significant effects of the tails on binding to
the cadherins. Using purified proteins, we show that desmosomal cadherins and
alpha-catenin compete directly for binding to plakoglobin, consistent with the
absence of alpha-catenin in desmosomes.
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