H-1, N-15 AND C-13 RESONANCE ASSIGNMENTS AND MONOMERIC STRUCTURE OF THE AMINO-TERMINAL EXTRACELLULAR DOMAIN OF EPITHELIAL CADHERIN

E-cadherin is a transmembrane protein that provides Ca2+-dependent cel l adhesion to epithelial cells. The large majority of the H-1, N-15, C -13 and (CO)-C-13 resonances of a 146-amino acid polypeptide from epit helial (E-) cadherin have been assigned using multidimensional NMR spe ctroscopy. The structure of the amino-terminal 100 amino acids, corres ponding to the first extracellular repeat of E-cadherin [Overduin et a l. (1995) Science, 267, 386-389], has been refined. The monomeric stat e of this isolated domain is demonstrated by light scattering and sedi mentation analysis. Seven beta-strands and two short helices were iden tified by patterns of NOE cross-beaks, vicinal coupling constants and chemical shift indices. A novel structural motif termed a quasi-beta-h elix found in the crystal structure of a neural (N-) cadherin domain [ Shapiro et al. (1995) Nature, 374, 327-337] is characterized in detail for the first time by NMR. Slowly exchanging amides were concentrated in the beta-sheet region and quasi-beta-helix. The beta-barrel fold o f the cadherin domain is topologically similar to the immunoglobulin f old. Comparison of this solution structure to the crystallized dimers of the N-terminal pair of E-cadherin domains [Nagar et al. (1996) Natu re, 380, 360-364] and of the homologous single domain of N-cadherin re veals a conserved cadherin fold with minor structural differences, whi ch can be accounted forby differences in metal ligation and oligomeric state.