Genome-wide structural analysis reveals novel membrane binding properties of AP180 N-terminal homology (ANTH) domains.
J Biol Chem
; 286(39): 34155-63, 2011 Sep 30.
Article
em En
| MEDLINE
| ID: mdl-21828048
ABSTRACT
An increasing number of cytosolic proteins are shown to interact with membrane lipids during diverse cellular processes, but computational prediction of these proteins and their membrane binding behaviors remains challenging. Here, we introduce a new combinatorial computation protocol for systematic and robust functional prediction of membrane-binding proteins through high throughput homology modeling and in-depth calculation of biophysical properties. The approach was applied to the genomic scale identification of the AP180 N-terminal homology (ANTH) domain, one of the modular lipid binding domains, and prediction of their membrane binding properties. Our analysis yielded comprehensive coverage of the ANTH domain family and allowed classification and functional annotation of proteins based on the differences in local structural and biophysical features. Our analysis also identified a group of plant ANTH domains with unique structural features that may confer novel functionalities. Experimental characterization of a representative member of this subfamily confirmed its unique membrane binding mechanism and unprecedented membrane deforming activity. Collectively, these studies suggest that our new computational approach can be applied to genome-wide functional prediction of other lipid binding domains.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Membrana Celular
/
Evolução Molecular
/
Proteínas Monoméricas de Montagem de Clatrina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos