View source for 7nd2


==Cryo-EM structure of the human FERRY complex==
<StructureSection load='7nd2' size='340' side='right'caption='[[7nd2]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7nd2]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ND2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ND2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7nd2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nd2 OCA], [https://pdbe.org/7nd2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nd2 RCSB], [https://www.ebi.ac.uk/pdbsum/7nd2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nd2 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PPR21_HUMAN PPR21_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/PPR21_HUMAN PPR21_HUMAN] Component of the FERRY complex (Five-subunit Endosomal Rab5 and RNA/ribosome intermediary) (PubMed:37267905, PubMed:37267906). The FERRY complex directly interacts with mRNAs and RAB5A, and functions as a RAB5A effector involved in the localization and the distribution of specific mRNAs most likely by mediating their endosomal transport. The complex recruits mRNAs and ribosomes to early endosomes through direct mRNA-interaction (PubMed:37267905). In the complex, PPP1R21 serves as a binding hub connecting all five complex subunits and mediating the binding to mRNA and early endosomes via RAB5A (PubMed:37267906). Putative regulator of protein phosphatase 1 (PP1) activity (PubMed:19389623). May play a role in the endosomal sorting process or in endosome maturation pathway (Probable) (PubMed:30520571).<ref>PMID:30520571</ref> <ref>PMID:37267905</ref> <ref>PMID:37267906</ref> <ref>PMID:19389623</ref> 
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== Publication Abstract from PubMed ==
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.

Structural basis of mRNA binding by the human FERRY Rab5 effector complex.,Quentin D, Schuhmacher JS, Klink BU, Lauer J, Shaikh TR, Huis In 't Veld PJ, Welp LM, Urlaub H, Zerial M, Raunser S Mol Cell. 2023 Jun 1;83(11):1856-1871.e9. doi: 10.1016/j.molcel.2023.05.009. PMID:37267906<ref>PMID:37267906</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7nd2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Klink BU]]
[[Category: Quentin D]]
[[Category: Raunser S]]