Dynamics-Driven Allostery in Protein Kinases.
Trends Biochem Sci
; 40(11): 628-647, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26481499
ABSTRACT
Protein kinases have very dynamic structures and their functionality strongly depends on their dynamic state. Active kinases reveal a dynamic pattern with residues clustering into semirigid communities that move in µs-ms timescale. Previously detected hydrophobic spines serve as connectors between communities. Communities do not follow the traditional subdomain structure of the kinase core or its secondary structure elements. Instead they are organized around main functional units. Integration of the communities depends on the assembly of the hydrophobic spine and phosphorylation of the activation loop. Single mutations can significantly disrupt the dynamic infrastructure and thereby interfere with long-distance allosteric signaling that propagates throughout the whole molecule. Dynamics is proposed to be the underlying mechanism for allosteric regulation in protein kinases.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
Idioma:
En
Revista:
Trends Biochem Sci
Ano de publicação:
2015
Tipo de documento:
Article