7ND2

Cryo-EM structure of the human FERRY complex

Summary for 7ND2

• Entry DOI: 10.2210/pdb7nd2/pdb
• EMDB information: 12273
• Descriptor: Protein phosphatase 1 regulatory subunit 21, Quinone oxidoreductase-like protein 1, Glutamine amidotransferase-like class 1 domain-containing protein 1 (3 entities in total)
• Functional Keywords: human ferry complex, five-subunit early endosome rna and ribosome intermediary complex, intracellular rna transport, early endosome-associated transport of rna, rna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 353838.45

Authors

Quentin, D.,Klink, B.U.,Raunser, S. (deposition date: 2021-01-29, release date: 2022-03-02, Last modification date: 2024-07-10)

Primary citation

Quentin, D.,Schuhmacher, J.S.,Klink, B.U.,Lauer, J.,Shaikh, T.R.,Huis In 't Veld, P.J.,Welp, L.M.,Urlaub, H.,Zerial, M.,Raunser, S.
Structural basis of mRNA binding by the human FERRY Rab5 effector complex.
Mol.Cell, 83:1856-1871.e9, 2023

PubMed 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.

PubMed: 37267906
DOI: 10.1016/j.molcel.2023.05.009

Experimental method

ELECTRON MICROSCOPY (4 Å)