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Structure of the human FERRY Rab5 effector complex

ABSTRACT: Long-range mRNA transport is crucial for the spatio-temporal regulation of gene expression, and its malfunction is linked to neurological disorders. The pentameric FERRY Rab5 effector complex is the molecular link between mRNA and the early endosome 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, in which two arm-like appendages, each consisting of Fy-2 and a Fy-5 dimer, protrude from the central Fy-4 dimer. We demonstrate that the coiled-coil domains of Fy-2 are flexible and project into opposite directions from the FERRY complex core. While the C-terminal coiled-coil acts as binding region for Fy-1/3 and Rab5, both coiled-coils together with Fy-5 bind mRNA. Thus, Fy-2 serves as binding hub that connects not only all five complex subunits, but also mediates the binding to mRNA and to the early endosome via Rab5. The FERRY structure provides novel mechanistic insight into long-distance mRNA transport.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Luisa Welp

LAB HEAD: Henning Urlaub

PROVIDER: PXD034875 | Pride | 2023-10-23

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	FERRY_EDC_PLinkReports.zip	Other
	FERRY_UV_proteinRNAcrosslinkReports.zip	Other
	MR_LW_J_Schuhmacher_290921_011021_XL_FERRY_EDC_bRP_rep1_1.mgf	Mgf
	MR_LW_J_Schuhmacher_290921_011021_XL_FERRY_EDC_bRP_rep1_1.raw	Raw
	MR_LW_J_Schuhmacher_290921_011021_XL_FERRY_EDC_bRP_rep1_10.mgf	Mgf

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