Structural basis of mRNA binding by the human FERRY Rab5 effector complex.
Mol Cell
; 83(11): 1856-1871.e9, 2023 06 01.
Article
em En
| MEDLINE
| ID: mdl-37267906
ABSTRACT
The pentameric FERRY Rab5 effector complex is a molecular link between mRNA and early endosomes in mRNA intracellular distribution. Here, we determine the cryo-EM structure of human FERRY. It reveals a unique clamp-like architecture that bears no resemblance to any known structure of Rab effectors. A combination of functional and mutational studies reveals that while the Fy-2 C-terminal coiled-coil acts as binding region for Fy-1/3 and Rab5, both coiled-coils and Fy-5 concur to bind mRNA. Mutations causing truncations of Fy-2 in patients with neurological disorders impair Rab5 binding or FERRY complex assembly. Thus, Fy-2 serves as a binding hub connecting all five complex subunits and mediating the binding to mRNA and early endosomes via Rab5. Our study provides mechanistic insights into long-distance mRNA transport and demonstrates that the particular architecture of FERRY is closely linked to a previously undescribed mode of RNA binding, involving coiled-coil domains.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas rab5 de Ligação ao GTP
/
Proteínas de Transporte Vesicular
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Alemanha