PDBsum entry 2o72

Cell adhesion, metal binding protein

PDB id: 2o72

Contents

Protein chain

213 a.a. *

Metals

_CA ×5

Waters ×245

* Residue conservation analysis

PDB id:

2o72

Name:

Cell adhesion, metal binding protein

Title:

Crystal structure analysis of human e-cadherin (1-213)

Structure:

Epithelial-cadherin. Chain: a. Fragment: n-terminal domains 1 and 2, residues 155-317. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdh1, cdhe, uvo. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.00Å R-factor: 0.193 R-free: 0.234

Authors:

E.Parisini,J.-H.Wang

Key ref:

E.Parisini et al. (2007). The Crystal Structure of Human E-cadherin Domains 1 and 2, and Comparison with other Cadherins in the Context of Adhesion Mechanism. J Mol Biol, 373, 401-411. PubMed id: 17850815 DOI: 10.1016/j.jmb.2007.08.011

Date:

09-Dec-06 Release date: 09-Oct-07

Protein chain

P12830  (CADH1_HUMAN) -  Cadherin-1 from Homo sapiens

Seq: 882 a.a.

Struc: 213 a.a.*

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

DOI no: 10.1016/j.jmb.2007.08.011

J Mol Biol 373:401-411 (2007)

PubMed id: 17850815

The Crystal Structure of Human E-cadherin Domains 1 and 2, and Comparison with other Cadherins in the Context of Adhesion Mechanism.

E.Parisini, J.M.Higgins, J.H.Liu, M.B.Brenner, J.H.Wang.

ABSTRACT

Cell adhesion mediated by type I cadherins involves homophilic "trans" interactions that are thought to be brought about by a strand exchange mechanism involving the N-terminal extracellular domain. Here, we present the high-resolution crystal structure of the N-terminal two domains of human E-cadherin. Comparison of this structure with other type I cadherin structures reveals features that are likely to be critical to facilitate dimerization by strand exchange as well as dimer flexibility. We integrate this structural knowledge to provide a model for type I cadherin adhesive interactions. Intra-molecular docking of the conserved N-terminal "adhesion arm" into the acceptor pocket in monomeric E-cadherin appears largely identical to inter-molecular docking of the adhesion arm in adhesive trans dimers. A strained conformation of the adhesion arm in the monomer, however, may create an equilibrium between "open" and "closed" forms that primes the cadherin for formation of adhesive interactions, which are then stabilized by additional dimer-specific contacts. By contrast, in type II cadherins, strain in the adhesion arm appears absent and a much larger surface area is involved in trans adhesion, which may compensate the activation energy required to peel off the intra-molecularly docked arm. It seems that evolution has selected slightly different adhesion mechanisms for type I and type II cadherins.

Selected figure(s)

Figure 2.
Figure 2. Detailed interactions between the N-terminal portion of molecule A (magenta) and the hydrophobic acceptor pocket of molecule B (green) within a strand-dimer. Broken lines show the salt bridge between the N-terminal ^AAsp1-NH[3]^+ and ^BGlu89 as well as the hydrogen bond between N^εH of ^ATrp2 and the carbonyl group of ^BAsp90. The stacking arrangement of residues ^BGlu89, ^ATrp2 and ^BMet92 (see inset on top left corner) is also likely to contribute to the stabilization of this “key-keyhole” interaction observed in all cadherin structures.

Figure 4.
Figure 4. Variable conformation of the N-terminal adhesion arm. (a) Superposition of the EC1 domains of human E-cadherin EC1–EC2 (adhesive form; green), mouse E-cadherin EC1–EC2 (closed; 1FF5, yellow), Xenopus C-cadherin EC1–EC5 (adhesive; 1L3W, light grey) and mouse E-cadherin EC1–EC2 adhesive form (1Q1P, red). The major portion of these molecules is well superimposed. By striking contrast, there is a spectrum of variable swing angles in their N-terminal segments. Such conformational variability suggests that this region confers necessary flexibility to the cadherin molecule to facilitate cell adhesion. (b) Superposition of the human E-cadherin EC1–EC2 structure (green) and the mouse E-cadherin EC1–EC2 structure (1Q1P, red), highlighting the orientation variation of their strand-dimer counterparts (magenta and yellow, respectively). The calcium ions present in all structures are omitted for clarity. (c) Detail of the hydrophobic interactions of Ile4 in the closed form of mouse E-cadherin (1FF5, pale yellow). (d) As for (c) but showing the adhesive dimer of human E-cadherin (green and magenta). (e) As for (d) but showing the adhesive dimer of mouse E-cadherin (1Q1P, red and yellow).

The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2007, 373, 401-411) copyright 2007.

Figures were selected by an automated process.