The crystal structure of the ligand binding module of axonin-1/TAG-1 suggests a zipper mechanism for neural cell adhesion

We have determined the crystal structure of the ligand binding fragment of the neural cell adhesion molecule axonin-1/TAG-1 comprising the first four immunoglobulin (Ig) domains. The overall structure of axonin-1(Ig1-4) is U- shaped due to contacts between domains 1 and 4 and domains 2 and 3. In the crystals, these molecules are aligned in a string with adjacent molecules o riented in an anti-parallel fashion and their C termini perpendicular to th e string. This arrangement suggests that cell adhesion by hemophilic axonin -1 interaction occurs by the formation of a linear zipper-like array in whi ch the axonin-1 molecules are alternately provided by the two apposed membr anes. In accordance with this model, mutations in a loop critical for the f ormation of the zipper resulted in the loss of the hemophilic binding capac ity of axonin-1.