Transient Structural Properties of the Rho GDP-Dissociation Inhibitor.
Angew Chem Int Ed Engl
; 63(34): e202403941, 2024 Aug 19.
Article
em En
| MEDLINE
| ID: mdl-38853146
ABSTRACT
Rho GTPases, master spatial regulators of a wide range of cellular processes, are orchestrated by complex formation with guanine nucleotide dissociation inhibitors (RhoGDIs). These have been thought to possess an unstructured N-terminus that inhibits nucleotide exchange of their client upon binding/folding. Via NMR analyses, molecular dynamics simulations, and biochemical assays, we reveal instead pertinent structural properties transiently maintained both, in the presence and absence of the client, imposed onto the terminus context-specifically by modulating interactions with the surface of the folded C-terminal domain. These observations revise the long-standing textbook picture of the GTPases' mechanism of membrane extraction. Rather than by a disorder-to-order transition upon binding of an inhibitory peptide, the intricate and highly selective extraction process of RhoGTPases is orchestrated via a dynamic ensemble bearing preformed transient structural properties, suitably modulated by the specific surrounding along the multi-step process.
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Base de dados:
MEDLINE
Assunto principal:
Simulação de Dinâmica Molecular
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article