Structure and interactions of NCAM Ig1-2-3 suggest a novel zipper mechanism for homophilic adhesion.
The neural cell adhesion molecule, NCAM, mediates Ca(2+)-independent cell-cell and cell-substratum adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM molecules) binding. NCAM plays a key role in neural development, regeneration, and synaptic plasticity, including learning and memory consolidation. The crystal structure of a fragment comprising the three N-terminal Ig modules of rat NCAM has been determined to 2.0 A resolution. Based on crystallographic data and biological experiments we present a novel model for NCAM homophilic binding. The Ig1 and Ig2 modules mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), whereas the Ig3 module mediates interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through simultaneous binding to the Ig1 and Ig2 modules. This arrangement results in two perpendicular zippers forming a double zipper-like NCAM adhesion complex.
Soroka
Vladislav
V
Protein Laboratory, Institute of Molecular Pathology, Panum Institute, Blegdamsvej 3 C, DK-2200 Copenhagen, Denmark.
Kolkova
Kateryna
K
Kastrup
Jette S
JS
Diederichs
Kay
K
Breed
Jason
J
Kiselyov
Vladislav V
VV
Poulsen
Flemming M
FM
Larsen
Ingrid K
IK
Welte
Wolfram
W
Berezin
Vladimir
V
Bock
Elisabeth
E
Kasper
Christina
C
D000906:Antibodies / Q000276:immunology* / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D018360:Crystallography, X-Ray; D019281:Dimerization; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D016501:Neurites / Q000502:physiology
D000906:Antibodies; D019006:Neural Cell Adhesion Molecules