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PDBsum entry 4zmo
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Cell adhesion
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PDB id
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4zmo
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References listed in PDB file
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Key reference
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Title
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Adhesive dimerization of human p-Cadherin catalyzed by a chaperone-Like mechanism.
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Authors
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S.Kudo,
J.M.Caaveiro,
K.Tsumoto.
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Ref.
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Structure, 2016,
24,
1523-1536.
[DOI no: ]
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PubMed id
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Abstract
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Orderly assembly of classical cadherins governs cell adhesion and tissue
maintenance. A key event is the strand-swap dimerization of the extracellular
ectodomains of two cadherin molecules from apposing cells. Here we have
determined crystal structures of P-cadherin in six different conformational
states to elaborate a motion picture of its adhesive dimerization at the atomic
level. The snapshots revealed that cell-adhesive dimerization is facilitated by
several intermediate states collectively termed X-dimer in analogy to other
classical cadherins. Based on previous studies and on the combined structural,
kinetic, thermodynamic, biochemical, and cellular data reported herein, we
propose that the adhesive dimerization of human P-cadherin is achieved by a
stepwise mechanism analogous to that of assembly chaperones. This mechanism,
applicable to type I classical cadherins, confers high specificity and fast
association rates. We expect these findings to guide innovative therapeutic
approaches targeting P-cadherin in cancer.
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