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*

proteins that participate in the organization of epithelial and endo-thelial junctions.Nectins have three Ig-like domains in the extracel-lular region, and the first one is essential in cell-cell adhesion and plays a central role in the interactionwith 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 iden-tified. Necl-1 is specifically expressed in neural tissue, has Ca2-independent homophilic and heterophilic cell-cell adhesion activ-ity, 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 Å, providing insight into trans-cellular recognitionmediated byNecl-1. The pro-tein crystallized as a dimer, and the dimeric form was confirmed by size-exclusion chromatography and chemical cross-linking experi-ments, indicating this V domain is sufficient for homophilic inter