2V37

Solution structure of the N-terminal extracellular domain of human T- cadherin

Summary for 2V37

• Entry DOI: 10.2210/pdb2v37/pdb
• NMR Information: BMRB: 7268
• Descriptor: CADHERIN-13 (1 entity in total)
• Functional Keywords: lipoprotein, polymorphism, glycoprotein, cell adhesion, adiponectin receptor, extracellular protein, calcium, membrane, t-cadherin, gpi-anchor, classical cadherin, cell-cell adhesion, cleavage on pair of basic residues
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cell membrane; Lipid-anchor, GPI-anchor: P55290
• Total number of polymer chains: 1
• Total formula weight: 11755.24

Authors

Dames, S.A.,Bang, E.J.,Ahrens, T.,Haeussinger, D.,Grzesiek, S. (deposition date: 2007-06-13, release date: 2008-06-10, Last modification date: 2024-05-15)

Primary citation

Dames, S.A.,Bang, E.,Haussinger, D.,Ahrens, T.,Engel, J.,Grzesiek, S.
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, 2008

PubMed 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.

PubMed: 18550521
DOI: 10.1074/jbc.M708335200

Experimental method

SOLUTION NMR