The crystal structure of the ligand-binding module of human TAG-1 suggests a new mode of homophilic interaction.
Human TAG-1 is a neural cell adhesion molecule that is crucial for the development of the nervous system during embryogenesis. It consists of six immunoglobulin-like and four fibronectin III-like domains and is anchored to the membrane by glycosylphosphatidylinositol. Herein we present the crystal structure of the four N-terminal immunoglobulin-like domains of TAG-1 (TAG-1(Ig1-4)), known to be important in heterophilic and homophilic macromolecular interactions. The contacts of neighboring molecules within the crystal were investigated. A comparison with the structure of the chicken ortholog resulted in an alternative mode for the molecular mechanism of homophilic TAG-1 interaction. This mode of TAG-1 homophilic interaction is based on dimer formation rather than formation of a molecular zipper as proposed for the chicken ortholog.
Mörtl
Mario
M
University of Konstanz, Department of Biology, Konstanz, Germany.
Sonderegger
Peter
P
Diederichs
Kay
K
Welte
Wolfram
W
D000818:Animals; D030161:Avian Proteins / Q000737:chemistry; D001665:Binding Sites; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D002645:Chickens; D058969:Contactin 2; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D030161:Avian Proteins; C548674:CNTN2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; D058969:Contactin 2; D008024:Ligands