Identification and characterization of the X-dimer of human P-cadherin: Implications for homophilic cell adhesion

Shota Kudo, Jose Manuel Martinez Caaveiro, Shuichiro Goda, Satoru Nagatoishi, Keisuke Ishii, Tadashi Matsuura, Yukio Sudou, Tatsuhiko Kodama, Takao Hamakubo, Kouhei Tsumoto

Research output: Contribution to journalArticle

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Abstract

Cell adhesion mediated by cadherins depends critically on the homophilic trans-dimerization of cadherin monomers from apposing cells, generating the so-called strand-swap dimer (ss-dimer). Recent evidence indicates that the ss-dimer is preceded by an intermediate species known as the X-dimer. Until now, the stabilized form of the X-dimer had only been observed in E-cadherin among the classical type I cadherins. Herein, we report the isolation and characterization of the analogous X-dimer of human P-cadherin. Small-angle X-ray scattering (SAXS) and site-directed mutagenesis data indicates that the overall architecture of the X-dimer of human P-cadherin is similar to that of E-cadherin. The X-dimerization is triggered by Ca 2+ and governed by specific protein-protein interactions. The attachment of three molecules of Ca 2+ with high affinity (K d = 9 ÎM) stabilizes the monomeric conformation of P-cadherin (Delta;T m = 17 °C). The Ca 2+ -stabilized monomer subsequently dimerizes in the X-configuration by establishing protein-protein interactions that require the first two extracellular domains of the cadherin. The homophilic X-dimerization is very specific, as the presence of the highly homologous E-cadherin does not interfere with the self-recognition of P-cadherin. These data suggest that the X-dimer could play a key role in the specific cell-cell adhesion mediated by human P-cadherin.

Original languageEnglish
Pages (from-to)1742-1752
Number of pages11
JournalBiochemistry
Volume53
Issue number11
DOIs
Publication statusPublished - Mar 25 2014
Externally publishedYes

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Cell adhesion
Cadherins
Cell Adhesion
Dimerization
Dimers
iocarmate meglumine
Proteins
Monomers
Mutagenesis
Site-Directed Mutagenesis
X ray scattering
Conformations
X-Rays

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Identification and characterization of the X-dimer of human P-cadherin : Implications for homophilic cell adhesion. / Kudo, Shota; Martinez Caaveiro, Jose Manuel; Goda, Shuichiro; Nagatoishi, Satoru; Ishii, Keisuke; Matsuura, Tadashi; Sudou, Yukio; Kodama, Tatsuhiko; Hamakubo, Takao; Tsumoto, Kouhei.

In: Biochemistry, Vol. 53, No. 11, 25.03.2014, p. 1742-1752.

Research output: Contribution to journalArticle

Kudo, S, Martinez Caaveiro, JM, Goda, S, Nagatoishi, S, Ishii, K, Matsuura, T, Sudou, Y, Kodama, T, Hamakubo, T & Tsumoto, K 2014, 'Identification and characterization of the X-dimer of human P-cadherin: Implications for homophilic cell adhesion', Biochemistry, vol. 53, no. 11, pp. 1742-1752. https://doi.org/10.1021/bi401341g
Kudo, Shota ; Martinez Caaveiro, Jose Manuel ; Goda, Shuichiro ; Nagatoishi, Satoru ; Ishii, Keisuke ; Matsuura, Tadashi ; Sudou, Yukio ; Kodama, Tatsuhiko ; Hamakubo, Takao ; Tsumoto, Kouhei. / Identification and characterization of the X-dimer of human P-cadherin : Implications for homophilic cell adhesion. In: Biochemistry. 2014 ; Vol. 53, No. 11. pp. 1742-1752.
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