The macromolecular architecture of extracellular domain of alphaNRXN1: domain organization, flexibility, and insights into trans-synaptic disposition.
Structure
; 18(8): 1044-53, 2010 Aug 11.
Article
em En
| MEDLINE
| ID: mdl-20696403
ABSTRACT
Neurexins are multidomain synaptic cell-adhesion proteins that associate with multiple partnering proteins. Genetic evidence indicates that neurexins may contribute to autism, schizophrenia, and nicotine dependence. Using analytical ultracentrifugation, single-particle electron microscopy, and solution X-ray scattering, we obtained a three-dimensional structural model of the entire extracellular domain of neurexin-1alpha. This protein adopts a dimensionally asymmetric conformation that is monomeric in solution, with a maximum dimension of approximately 170 A. The extracellular domain of alpha-neurexin maintains a characteristic "Y" shape, whereby LNS domains 1-4 form an extended base of the "Y" and LNS5-6 the shorter arms. Moreover, two major regions of flexibility are present one between EGF1 and LNS2, corresponding to splice site 1, another between LNS5 and 6. We thus provide the first structural insights into the architecture of the extracellular region of neurexin-1alpha, show how the protein may fit in the synaptic cleft, and how partnering proteins could bind simultaneously.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Conformação Proteica
/
Sinapses
/
Modelos Moleculares
/
Moléculas de Adesão Celular Neuronais
/
Estrutura Terciária de Proteína
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Structure
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos