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 oriented in an anti-parallel fashion and their C termini perpendicular to the string. This arrangement suggests that cell adhesion by homophilic axonin-1 interaction occurs by the formation of a linear zipper-like array in which the axonin-1 molecules are alternately provided by the two apposed membranes. In accordance with this model, mutations in a loop critical for the formation of the zipper resulted in the loss of the homophilic binding capacity of axonin-1.
Freigang
J
J
Faculty of Biology, University of Konstanz, Germany.
Proba
K
K
Leder
L
L
Diederichs
K
K
Sonderegger
P
P
Welte
W
W
D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry* / Q000378:metabolism; D058969:Contactin 2; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011485:Protein Binding; D011487:Protein Conformation; D014407:Tumor Cells, Cultured
C548674:CNTN2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; D058969:Contactin 2; D008024:Ligands