PDBsum entry 1ncj

Cell adhesion protein

PDB id: 1ncj

Contents

Protein chain

214 a.a. *

Metals

IUM

_CA ×3

* Residue conservation analysis

PDB id:

1ncj

Name:

Cell adhesion protein

Title:

N-cadherin, two-domain fragment

Structure:

Protein (n-cadherin). Chain: a. Fragment: two-domain fragment. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Tissue: brain. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.40Å R-factor: 0.212 R-free: 0.321

Authors:

K.Tamura,W.-S.Shan,W.A.Hendrickson,D.R.Colman,L.Shapiro

Key ref:

K.Tamura et al. (1998). Structure-function analysis of cell adhesion by neural (N-) cadherin. Neuron, 20, 1153-1163. PubMed id: 9655503 DOI: 10.1016/S0896-6273(00)80496-1

Date:

02-Feb-99 Release date: 18-Mar-99

Protein chain

P15116  (CADH2_MOUSE) -  Cadherin-2 from Mus musculus

Seq: 906 a.a.

Struc: 214 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/S0896-6273(00)80496-1

Neuron 20:1153-1163 (1998)

PubMed id: 9655503

Structure-function analysis of cell adhesion by neural (N-) cadherin.

K.Tamura, W.S.Shan, W.A.Hendrickson, D.R.Colman, L.Shapiro.

ABSTRACT

To investigate the possible biological function of the lateral "strand dimer" observed in crystal structures of a D1 domain extracellular fragment from N-cadherin, we have undertaken site-directed mutagenesis studies of this molecule. Mutation of most residues important in the strand dimer interface abolish the ability of N-cadherin to mediate cell adhesion. Mutation of an analogous central residue (Trp-2) in E-cadherin also abrogates the adhesive capacity of that molecule. We also determined the crystal structure of a Ca2+-complexed two-domain fragment from N-cadherin. This structure, like its E-cadherin counterpart, does not adopt the strand dimer conformation. This suggests the possibility that classical cadherins might stably exist in both dimeric and monomeric forms. Data from several laboratories imply that lateral dimerization or clustering of cadherins may increase their adhesivity. We suggest the possibility that the strand dimer may play a role in this activation.

Selected figure(s)

Figure 1.
Figure 1. Backbone Worm Diagram of Two N-Cadherin D1 Molecules and Molecular Details of the Strand Dimer Interaction(A) Backbone worm diagram of two N-cadherin D1 molecules involved in strand dimer pairing (from the crystal structure with Protein Data Bank accession code 1NCG). Only the side chain from Trp-2 is shown; the N and C termini are noted, and calcium-analog ytterbium ions are shown as pink spheres.(B) Molecular details of the strand dimer interaction. The A strand of one protomer is colored in green; for clarity, the rest of this protomer is not displayed. Residues that line the Trp-2 acceptor pocket are colored in blue. Residue positions that we have mutated in this paper are underlined in red. His-79 and Val-81 are colored gold; they have been implicated in prior studies as residues important for adhesion.

Figure 6.
Figure 6. Structure of Two-Domain N-Cadherin and Comparison of Strand Dimer Surfaces(A) Stereo view of a representative region from the electron density map calculated with 2|F[o] − F[c]| coefficients contoured at 1.0 σ (blue). A portion of the Bijvoet difference Fourier map for the selenomethionyl protein, contoured at 5.0 σ, is shown in cyan. The position of the peak in this map corresponds to the position of the selenium atom from selenomethionine 128.(B) α-carbon trace of the refined N-cadherin D1D2 protomer superimposed on the Bijvoet difference Fourier map contoured at 5.0 σ. The position of the selenium atom from every selenomethionine residue in the protein is clearly seen in the difference map, and these positions match the refined model. “U” marks the site of a uranyl ion, which also has anomalous diffraction properties at the selenium edge energy. Figure prepared with the program TOM ([11]).(C) Ca^2+-binding site of N-cadherin D1D2. Each amino acid that donates ligands from its side chain is labeled; Bonds to oxygen atoms are shown in red, nitrogen atoms are shown in blue, and Ca^2+ ions are drawn as green spheres. Figure prepared with SETOR ([6]).(D) Crystal interface [(x,1 − y,1 − z) symmetry mate in space group I422] that shows an antiparallel interaction at the adhesive face of the D1 domain of N-cadherin. This interface has similarities to, yet is distinct from, the putative adhesive interface suggested previously ([26]). Inset shows a close-up view of this interface. Interactions between side chains are almost exclusively hydrophobic. Figure prepared with GRASP ( [17]).(E) Superposition of N-cadherin (white) with E-cadherin (orange). The D2 domains have been superposed, illustrating the relative motions between domains as displacemant of the D1 domain.(F) Molecular surface of one monomer of N-cadherin with the part of the A strand from its strand dimer partner drawn as a stick model (from Protein Data Bank accession 1NCG). Note the complete intercalation of the Trp-2 side chain.(G) Molecular surfaces of N- and E-cadherin crystal structures. Convex surface features are drawn in green, and concave features are drawn in gray. The arrows point to the Trp-2 acceptor pocket, which is a conserved structural feature of the one-domain N-cadherin structures ([26]), two-domain N-cadherin structure (this work), and two-domain E-cadherin structure ( [16]). Figure prepared with GRASP ( [17]).

The above figures are reprinted by permission from Cell Press: Neuron (1998, 20, 1153-1163) copyright 1998.

Figures were selected by an automated process.