title: Structure and interactions of NCAM Ig1-2-3 suggest a novel zipper mechanism for homophilic adhesion.
abstract: 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.
authors.affiliation: Protein Laboratory, Institute of Molecular Pathology, Panum Institute, Blegdamsvej 3 C, DK-2200 Copenhagen, Denmark.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Soroka
authors.forename: Kateryna
authors.initials: K
authors.lastname: Kolkova
authors.forename: Jette S
authors.initials: JS
authors.lastname: Kastrup
authors.forename: Kay
authors.initials: K
authors.lastname: Diederichs
authors.forename: Jason
authors.initials: J
authors.lastname: Breed
authors.forename: Vladislav V
authors.initials: VV
authors.lastname: Kiselyov
authors.forename: Flemming M
authors.initials: FM
authors.lastname: Poulsen
authors.forename: Ingrid K
authors.initials: IK
authors.lastname: Larsen
authors.forename: Wolfram
authors.initials: W
authors.lastname: Welte
authors.forename: Vladimir
authors.initials: V
authors.lastname: Berezin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bock
authors.forename: Christina
authors.initials: C
authors.lastname: Kasper
mesh_terms: 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
chemical_list: D000906:Antibodies; D019006:Neural Cell Adhesion Molecules