1FF5

STRUCTURE OF E-CADHERIN DOUBLE DOMAIN

Summary for 1FF5

• Entry DOI: 10.2210/pdb1ff5/pdb
• Related: 1EDH 1NCG 1NCH 1NCJ 1SHU
• Descriptor: EPITHELIAL CADHERIN, CALCIUM ION (3 entities in total)
• Functional Keywords: e-cadherin, ca-binding, cell adhesion
• Biological source: Mus musculus (house mouse)
• Cellular location: Cell junction : P09803
• Total number of polymer chains: 2
• Total formula weight: 48079.65

Authors

Pertz, O.,Bozic, D.,Koch, A.W.,Fauser, C.,Brancaccio, A.,Engel, J. (deposition date: 2000-07-25, release date: 2000-08-23, Last modification date: 2024-05-22)

Primary citation

Pertz, O.,Bozic, D.,Koch, A.W.,Fauser, C.,Brancaccio, A.,Engel, J.
A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E-cadherin homoassociation.
EMBO J., 18:1738-1747, 1999

PubMed 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.

PubMed: 10202138
DOI: 10.1093/emboj/18.7.1738

Experimental method

X-RAY DIFFRACTION (2.93 Å)