Evolution of a Protein Interaction Domain Family by Tuning Conformational Flexibility.
J Am Chem Soc
; 138(46): 15150-15156, 2016 11 23.
Article
em En
| MEDLINE
| ID: mdl-27502157
ABSTRACT
Conformational flexibility allows proteins to adopt multiple functionally important conformations but can also lead to nonfunctional structures. We analyzed the dynamic behavior of the enzyme guanylate kinase as it evolved into the GK protein interaction domain (GKPID) to investigate the role of flexibility in the evolution of new protein functions. We found that the ancestral enzyme is very flexible, allowing it to adopt open conformations that can bind nucleotide and closed ones that enable catalysis of phosphotransfer from ATP to GMP. Historical mutations that converted the GK from an enzyme to a protein interaction domain dramatically reduce flexibility, predominantly by inhibiting rotations of the protein backbone that are coupled to the global closing motion. Removing flexibility prevents adoption of conformations that cannot fit the protein partner in the binding site. Our results highlight the importance of mutations that optimize protein conformational flexibility with function during evolution.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ressonância Magnética Nuclear Biomolecular
/
Guanilato Quinases
/
Domínios e Motivos de Interação entre Proteínas
/
Simulação de Dinâmica Molecular
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos