Genetic interaction mapping informs integrative structure determination of protein complexes.
Science
; 370(6522)2020 12 11.
Article
em En
| MEDLINE
| ID: mdl-33303586
ABSTRACT
Determining structures of protein complexes is crucial for understanding cellular functions. Here, we describe an integrative structure determination approach that relies on in vivo measurements of genetic interactions. We construct phenotypic profiles for point mutations crossed against gene deletions or exposed to environmental perturbations, followed by converting similarities between two profiles into an upper bound on the distance between the mutated residues. We determine the structure of the yeast histone H3-H4 complex based on ~500,000 genetic interactions of 350 mutants. We then apply the method to subunits Rpb1-Rpb2 of yeast RNA polymerase II and subunits RpoB-RpoC of bacterial RNA polymerase. The accuracy is comparable to that based on chemical cross-links; using restraints from both genetic interactions and cross-links further improves model accuracy and precision. The approach provides an efficient means to augment integrative structure determination with in vivo observations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
/
Proteínas de Saccharomyces cerevisiae
/
Complexos Multiproteicos
/
Mapas de Interação de Proteínas
Idioma:
En
Revista:
Science
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos