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TitleStructural basis of mRNA binding by the human FERRY Rab5 effector complex.
Journal, issue, pagesMol Cell, Vol. 83, Issue 11, Page 1856-11871.e9, Year 2023
Publish dateJun 1, 2023
AuthorsDennis Quentin / Jan S Schuhmacher / Björn U Klink / Jeni Lauer / Tanvir R Shaikh / Pim J Huis In 't Veld / Luisa M Welp / Henning Urlaub / Marino Zerial / Stefan Raunser /
PubMed AbstractThe 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 ...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.
External linksMol Cell / PubMed:37267906
MethodsEM (single particle) / X-ray diffraction
Resolution2.7 - 4.0 Å
Structure data

12273

7nd2

EMDB-12273, PDB-7nd2:
Cryo-EM structure of the human FERRY complex
Method: EM (single particle) / Resolution: 4.0 Å

PDB-8a3o:
Structure of human Fy-4
Method: X-RAY DIFFRACTION / Resolution: 2.9 Å

PDB-8a3p:
Structure of human Fy-5.
Method: X-RAY DIFFRACTION / Resolution: 2.7 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsRNA BINDING PROTEIN / Human FERRY complex / Five-subunit Early endosome RNA and Ribosome intermediarY complex / Intracellular RNA transport / Early Endosome-associated transport of RNA / STRUCTURAL PROTEIN / FERRY complex / mRNA transport / Early endosome / RNA binding / RNA transport

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