1H, 15N and 13C resonance assignments and monomeric structure of the amino-terminal extracellular domain of epithelial cadherin.
E-cadherin is a transmembrane protein that provides Ca(2+)-dependent cell adhesion to epithelial cells. The large majority of the 1H, 15N, 13C and 13CO resonances of a 146-amino acid polypeptide from epithelial (E-) cadherin have been assigned using multidimensional NMR spectroscopy. The structure of the amino-terminal 100 amino acids, corresponding to the first extracellular repeat of E-cadherin [Overduin et al. (1995) Science, 267, 386-389], has been refined. The monomeric state of this isolated domain is demonstrated by light scattering and sedimentation analysis. Seven beta-strands and two short helices were identified by patterns of NOE cross-peaks, vicinal coupling constants and chemical shift indices. A novel structural motif termed a quasi-beta-helix 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 of the cadherin domain is topologically similar to the immunoglobulin fold. Comparison of this solution structure to the crystallized dimers of the N-terminal pair of E-cadherin domains [Nagar et al. (1996) Nature, 380, 360-364] and of the homologous single domain of N-cadherin reveals a conserved cadherin fold with minor structural differences, which can be accounted for by differences in metal ligation and oligomeric state.
Overduin
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Division of Molecular and Structural Biology, Ontario Cancer Institute, Toronto, Canada.
Tong
K I
KI
Kay
C M
CM
Ikura
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M
D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics; D002247:Carbon Isotopes; D006859:Hydrogen / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009587:Nitrogen Isotopes; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D015820:Cadherins; D002247:Carbon Isotopes; D009587:Nitrogen Isotopes; D006859:Hydrogen