title: Structural analysis of the synaptic protein neuroligin and its beta-neurexin complex: determinants for folding and cell adhesion.
abstract: The neuroligins are postsynaptic cell adhesion proteins whose associations with presynaptic neurexins participate in synaptogenesis. Mutations in the neuroligin and neurexin genes appear to be associated with autism and mental retardation. The crystal structure of a neuroligin reveals features not found in its catalytically active relatives, such as the fully hydrophobic interface forming the functional neuroligin dimer; the conformations of surface loops surrounding the vestigial active center; the location of determinants that are critical for folding and processing; and the absence of a macromolecular dipole and presence of an electronegative, hydrophilic surface for neurexin binding. The structure of a beta-neurexin-neuroligin complex reveals the precise orientation of the bound neurexin and, despite a limited resolution, provides substantial information on the Ca2+-dependent interactions network involved in trans-synaptic neurexin-neuroligin association. These structures exemplify how an alpha/beta-hydrolase fold varies in surface topography to confer adhesion properties and provide templates for analyzing abnormal processing or recognition events associated with autism.
authors: Biochimie des Interactions Moléculaires et Cellulaires, CNRS FRE-2738, Institut Fédératif de Recherche Jean Roche, Université de la Méditerranée, Faculté de Médecine Secteur Nord, F-13916 Marseille Cedex 20, France.
authors: Igor P
authors: IP
authors: Fabrichny
authors: Philippe
authors: P
authors: Leone
authors: Gerlind
authors: G
authors: Sulzenbacher
authors: Davide
authors: D
authors: Comoletti
authors: Meghan T
authors: MT
authors: Miller
authors: Palmer
authors: P
authors: Taylor
authors: Yves
authors: Y
authors: Bourne
authors: Pascale
authors: P
authors: Marchot
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002338:Carotenoids / Q000737:chemistry* / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002461:Cell Line, Transformed; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding / Q000502:physiology; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection / Q000379:methods
chemical_list: D008565:Membrane Proteins; D011994:Recombinant Proteins; D002338:Carotenoids; C099823:norbixin; D002118:Calcium