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.
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.
National Laboratory of Biomacromolecules, Institute of Biophysics (IBP), Chinese Academy of Sciences, Beijing 100101, China.
Xiuhua
X
Dong
Feng
F
Xu
Yanhua
Y
Gong
Jing
J
Gao
Peng
P
Lin
Tao
T
Chen
Ying
Y
Peng
Boqin
B
Qiang
Jiangang
J
Yuan
Xiaozhong
X
Peng
Zihe
Z
Rao
D000595:Amino Acid Sequence; D001369:Axons / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D002465:Cell Movement; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D003432:Cross-Linking Reagents / Q000494:pharmacology; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D016296:Mutagenesis; D000075983:Nectins; D010649:Phenylalanine / Q000737:chemistry; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000378:metabolism
C498599:CADM3 protein, human; D015815:Cell Adhesion Molecules; D003432:Cross-Linking Reagents; D007136:Immunoglobulins; D008565:Membrane Proteins; D000075983:Nectins; D011993:Recombinant Fusion Proteins; D010649:Phenylalanine