A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E-cadherin homoassociation
- PMID: 10202138
- PMCID: PMC1171260
- DOI: 10.1093/emboj/18.7.1738
A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E-cadherin homoassociation
Abstract
Electron microscopy of ECADCOMP, a recombinant E-cadherin ectodomain pentamerized by the assembly domain of cartilage oligomeric matrix protein, has been used to analyze the role of cis-dimerization and trans-interaction in the homophilic association of this cell adhesion molecule. The Ca2+ dependency of both interactions was investigated. Low Ca2+ concentrations (50 microM) stabilized the rod-like structure of E-cadherin. At medium Ca2+ concentration (500 microM), two adjacent ectodomains in a pentamer formed cis-dimers. At high Ca2+ concentration (>1 mM), two cis-dimers from different pentamers formed a trans-interaction. The X-ray structure of an N-terminal domain pair of E-cadherin revealed two molecules per asymmetric unit in an intertwisted X-shaped arrangement with closest contacts in the Ca2+-binding region between domains 1 and 2. Contrary to previous data, Trp2 was docked in the hydrophobic cavity of its own molecule, and was therefore not involved in cis-dimerization of two molecules. This was supported further by W2A and A80I (a residue involved in the hydrophobic cavity surrounding Trp2) mutations in ECADCOMP which both led to abrogation of the trans- but not the cis-interaction. Structural and biochemical data suggest a link between Ca2+ binding in the millimolar range and Trp2 docking, both events being essential for the trans-association.
Similar articles
-
Molecular evolution of the cadherin superfamily.Int J Biochem Cell Biol. 2009 Feb;41(2):349-69. doi: 10.1016/j.biocel.2008.09.027. Epub 2008 Oct 4. Int J Biochem Cell Biol. 2009. PMID: 18848899 Review.
-
The mechanism of cell adhesion by classical cadherins: the role of domain 1.J Cell Sci. 2005 Feb 15;118(Pt 4):711-21. doi: 10.1242/jcs.01665. Epub 2005 Jan 25. J Cell Sci. 2005. PMID: 15671061
-
The cadherin-catenin complex as a focal point of cell adhesion and signalling: new insights from three-dimensional structures.Bioessays. 2004 May;26(5):497-511. doi: 10.1002/bies.20033. Bioessays. 2004. PMID: 15112230 Review.
-
Calcium binding and homoassociation of E-cadherin domains.Biochemistry. 1997 Jun 24;36(25):7697-705. doi: 10.1021/bi9705624. Biochemistry. 1997. PMID: 9201910
-
Structural basis of calcium-induced E-cadherin rigidification and dimerization.Nature. 1996 Mar 28;380(6572):360-4. doi: 10.1038/380360a0. Nature. 1996. PMID: 8598933
Cited by
-
Reversible photoregulation of cell-cell adhesions with opto-E-cadherin.Nat Commun. 2023 Oct 9;14(1):6292. doi: 10.1038/s41467-023-41932-0. Nat Commun. 2023. PMID: 37813868 Free PMC article.
-
Transient interactions drive the lateral clustering of cadherin-23 on membrane.Commun Biol. 2023 Mar 18;6(1):293. doi: 10.1038/s42003-023-04677-6. Commun Biol. 2023. PMID: 36934176 Free PMC article.
-
Molecular mechanism for strengthening E-cadherin adhesion using a monoclonal antibody.Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2204473119. doi: 10.1073/pnas.2204473119. Epub 2022 Aug 3. Proc Natl Acad Sci U S A. 2022. PMID: 35921442 Free PMC article.
-
RapD Is a Multimeric Calcium-Binding Protein That Interacts With the Rhizobium leguminosarum Biofilm Exopolysaccharide, Influencing the Polymer Lengths.Front Microbiol. 2022 Jul 6;13:895526. doi: 10.3389/fmicb.2022.895526. eCollection 2022. Front Microbiol. 2022. PMID: 35875570 Free PMC article.
-
Multiple dimeric structures and strand-swap dimerization of E-cadherin in solution visualized by high-speed atomic force microscopy.Proc Natl Acad Sci U S A. 2022 Jul 26;119(30):e2208067119. doi: 10.1073/pnas.2208067119. Epub 2022 Jul 22. Proc Natl Acad Sci U S A. 2022. PMID: 35867820 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous