Structure of the human FERRY Rab5 effector complex
Quentin, D.; Schuhmacher, J.; Klink, B. U.; Lauer, J.; Shaikh, T.; Huis in 't Veld, P. J.; Welp, L. M.; Urlaub, H.; Zerial, M.; Raunser, S.
Show abstract
Long-range mRNA transport is crucial for the spatio-temporal regulation of gene expression, and its malfunction leads to neurological disorders. The pentameric FERRY Rab5 effector complex is the molecular link between mRNA and early endosomes in mRNA intracellular distribution. Here, we determine the cryo-EM structure of the human FERRY complex, composed of Fy-1 to Fy-5. The structure reveals a clamp-like architecture, where two arm-like appendages of Fy-2 and a Fy-5 dimer, protrude from the central Fy-4 dimer. The coiled-coil domains of Fy-2 are flexible and project into opposite directions from the core. 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. The FERRY structure provides novel mechanistic insights into long-distance mRNA transport.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM 96%
- Cryo-EM structures of the Caspase activated protein XKR9 involved in apoptotic lipid scrambling 96%
- Structural and mechanistic basis of the EMC-dependent biogenesis of distinct transmembrane clients 96%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.