View source for 8qcy


==Cryo-EM structure of the outward-facing FLVCR2==
<StructureSection load='8qcy' size='340' side='right'caption='[[8qcy]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8qcy]] is a 1 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=8QCY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QCY 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]] 2.9&#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=8qcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qcy OCA], [https://pdbe.org/8qcy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qcy RCSB], [https://www.ebi.ac.uk/pdbsum/8qcy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qcy ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FLVC2_HUMAN FLVC2_HUMAN] Fowler vasculopathy. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/FLVC2_HUMAN FLVC2_HUMAN] Putative heme b importer/sensor involved in heme homeostasis in response to the metabolic state of the cell and to diet. May act as a sensor of cytosolic and/or mitochondrial heme levels to regulate mitochondrial respiration processes, ATP synthesis and thermogenesis. At low heme levels, interacts with components of electron transfer chain (ETC) complexes and ATP2A2, leading to ubiquitin-mediated degradation of ATP2A2 and inhibition of thermogenesis. Upon heme binding, dissociates from ETC complexes to allow switching from mitochondrial ATP synthesis to thermogenesis. Alternatively, in coordination with ATP2A2 may mediate calcium transport and signaling in response to heme.<ref>PMID:20823265</ref> <ref>PMID:32973183</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily(1). Their dysfunction is linked to several clinical disorders, including PCARP, HSAN and Fowler syndrome(2-7). Earlier studies concluded that FLVCR1 may function as a haem exporter(8-12), whereas FLVCR2 was suggested to act as a haem importer(13), yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters(14-16). Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across the plasma membrane, using a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unravelled the coordination chemistry underlying their substrate interactions. Fully conserved tryptophan and tyrosine residues form the binding pocket of both transporters and confer selectivity for choline and ethanolamine through cation-pi interactions. Our findings clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhance our comprehension of disease-associated mutations that interfere with these vital processes and shed light on the conformational dynamics of these major facilitator superfamily proteins during the transport cycle.

Molecular mechanism of choline and ethanolamine transport in humans.,Ri K, Weng TH, Claveras Cabezudo A, Josting W, Zhang Y, Bazzone A, Leong NCP, Welsch S, Doty RT, Gursu G, Lim TJY, Schmidt SL, Abkowitz JL, Hummer G, Wu D, Nguyen LN, Safarian S Nature. 2024 May 22. doi: 10.1038/s41586-024-07444-7. PMID:38778100<ref>PMID:38778100</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8qcy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Safarian S]]
[[Category: Weng T-H]]
[[Category: Wu D]]