PDBsum entry 2v37

Cell adhesion

PDB id: 2v37

Contents

Protein chain

105 a.a. *

* Residue conservation analysis

PDB id:

2v37

Name:

Cell adhesion

Title:

Solution structure of the n-terminal extracellular domain of human t- cadherin

Structure:

Cadherin-13. Chain: a. Fragment: ec1, residues 139-243. Synonym: human t-cadherin, truncated-cadherin, t-cadherin, t-cad, heart-cadherin, h-cadherin, p105. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

S.A.Dames,E.J.Bang,T.Ahrens,D.Haeussinger,S.Grzesiek

Key ref:

S.A.Dames et al. (2008). Insights into the Low Adhesive Capacity of Human T-cadherin from the NMR Structure of Its N-terminal Extracellular Domain. J Biol Chem, 283, 23485-23495. PubMed id: 18550521 DOI: 10.1074/jbc.M708335200

Date:

13-Jun-07 Release date: 10-Jun-08

Protein chain

P55290  (CAD13_HUMAN) -  Cadherin-13 from Homo sapiens

Seq: 713 a.a.

Struc: 105 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M708335200

J Biol Chem 283:23485-23495 (2008)

PubMed id: 18550521

Insights into the Low Adhesive Capacity of Human T-cadherin from the NMR Structure of Its N-terminal Extracellular Domain.

S.A.Dames, E.Bang, D.Haüssinger, T.Ahrens, J.Engel, S.Grzesiek.

ABSTRACT

T-cadherin is unique among the family of type I cadherins, because it lacks transmembrane and cytosolic domains, and attaches to the membrane via a glycophosphoinositol anchor. The N-terminal cadherin repeat of T-cadherin (Tcad1) is approximately 30% identical to E-, N-, and other classical cadherins. However, it lacks many amino acids crucial for their adhesive function of classical cadherins. Among others, Trp-2, which is the key residue forming the canonical strand-exchange dimer, is replaced by an isoleucine. Here, we report the NMR structure of the first cadherin repeat of T-cadherin (Tcad1). Tcad1, as other cadherin domains, adopts a beta-barrel structure with a Greek key folding topology. However, Tcad1 is monomeric in the absence and presence of calcium. Accordingly, lle-2 binds into a hydrophobic pocket on the same protomer and participates in an N-terminal beta-sheet. Specific amino acid replacements compared to classical cadherins reduce the size of the binding pocket for residue 2 and alter the backbone conformation and flexibility around residues 5 and 15 as well as many electrostatic interactions. These modifications apparently stabilize the monomeric form and make it less susceptible to a conformational switch upon calcium binding. The absence of a tendency for homoassociation observed by NMR is consistent with electron microscopy and solid-phase binding data of the full T-cadherin ectodomain (Tcad1-5). The apparent low adhesiveness of T-cadherin suggests that it is likely to be involved in reversible and dynamic cellular adhesion-deadhesion processes, which are consistent with its role in cell growth and migration.

Selected figure(s)

Figure 2.
FIGURE 2. The NMR structure of Tcad1. Tcad1 adopts as the other characterized cadherin domains a β-barrel structure (A) with a Greek key folding topology (B). Open boxes mark residues with a β-bulge conformation. As Tcad1 is monomeric in the presence and absence of calcium, residues Ile-2-Val-3 and Val-25-Asp-26 can participate in a stable β-sheet structure (pink colored strands). The pairing of the strands is antiparallel except for the parallel arrangement of strands B and I. A stereoview of the superposition of the 20 final in a water shell refined structures is shown in C. The β-strands are colored as in A and B. Glycines with positive -angles are depicted in yellow and prolines that adopt a cis-peptide bond conformation in red. All structure pictures were made with the programs MolMol (49) and POV-Ray.

Figure 4.
FIGURE 4. Calcium binding to Tcad1. For this representation, the chemical shift changes in ^1H-^15N-HSQC of Tcad1 with different concentrations of Ca^2+ (supplemental Fig. S4) have been mapped onto a space-filling model of Tcad1 (middle and right). Strong (red) and weak (orange) chemical shift changes are observed only for residues in proximity to the calcium binding sites (residues with green colored side chains in the ribbon representation to the left, see also Fig. 1B). Residues colored in yellow shift only very weakly.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 23485-23495) copyright 2008.

Figures were selected by the author.