PDBsum entry 1z9m

Cell adhesion

PDB id: 1z9m

Contents

Protein chains

104 a.a. *

Waters ×196

* Residue conservation analysis

PDB id:

1z9m

Name:

Cell adhesion

Title:

Crystal structure of nectin-like molecule-1 protein domain 1

Structure:

Gapa225. Chain: a, b. Fragment: residues 37-141. Synonym: nectin-like molecule_1 domain 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

2.40Å R-factor: 0.227 R-free: 0.274

Authors:

X.Dong,F.Xu,Y.Gong,J.Gao,P.Lin,T.Chen,Y.Peng,B.Qiang,J.Yuan,X.Peng, Z.Rao

Key ref:

X.Dong et al. (2006). Crystal structure of the V domain of human Nectin-like molecule-1/Syncam3/Tsll1/Igsf4b, a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule. J Biol Chem, 281, 10610-10617. PubMed id: 16467305 DOI: 10.1074/jbc.M513459200

Date:

03-Apr-05 Release date: 07-Feb-06

Protein chains

Q8N126  (CADM3_HUMAN) -  Cell adhesion molecule 3 from Homo sapiens

Seq: 398 a.a.

Struc: 104 a.a.

DOI no: 10.1074/jbc.M513459200

J Biol Chem 281:10610-10617 (2006)

PubMed id: 16467305

Crystal structure of the V domain of human Nectin-like molecule-1/Syncam3/Tsll1/Igsf4b, a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule.

X.Dong, F.Xu, Y.Gong, J.Gao, P.Lin, T.Chen, Y.Peng, B.Qiang, J.Yuan, X.Peng, Z.Rao.

ABSTRACT

Nectins are Ca(2+)-independent immunoglobulin (Ig) superfamily proteins that participate in the organization of epithelial and endothelial junctions. Nectins have three Ig-like domains in the extracellular region, and the first one is essential in cell-cell adhesion and plays a central role in the interaction with the envelope glycoprotein D of several viruses. Five Nectin-like molecules (Necl-1 through -5) with similar domain structures to those of Nectins have been identified. Necl-1 is specifically expressed in neural tissue, has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity, and plays an important role in the formation of synapses, axon bundles, and myelinated axons. Here we report the first crystal structure of its N-terminal Ig-like V domain at 2.4 A, providing insight into trans-cellular recognition mediated by Necl-1. The protein crystallized as a dimer, and the dimeric form was confirmed by size-exclusion chromatography and chemical cross-linking experiments, indicating this V domain is sufficient for homophilic interaction. Mutagenesis work demonstrated that Phe(82) is a key residue for the adhesion activity of Necl-1. A model for homophilic adhesion of Necl-1 at synapses is proposed based on its structure and previous studies.

Selected figure(s)

Figure 4.
FIGURE 4. A, surface representation of the Necl-1 V domain monomer. Hydrophobic residues are shown in white, acidic residues in red, and basic residues in blue. Hydrophobic interactions should be the main force in dimerization. B, the homophilic binding interface of Necl-1 V domain. One Necl-1 V monomer is shown in surface representation, and the other is shown as a pink ribbon. The interface is formed mainly by C-C'-C''-D -strands and intervening loops.

Figure 8.
FIGURE 8. Schematic representation of the proposed mechanism of homophilic adhesion mediated by Necl-1 at synapses, based on the crystal structure. The cell surfaces are shown in green with Necl-1 protruding from them. The Necl-1 monomers, shown on the left, first form cis-dimers, and then form trans-dimers, eventually causing cell-cell adhesion (shown on the right).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 10610-10617) copyright 2006.

Figures were selected by an automated process.