View source for 8ubw


==Choline-bound FLVCR1==
<StructureSection load='8ubw' size='340' side='right'caption='[[8ubw]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ubw]] 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=8UBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UBW 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]] 2.59&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CHT:CHOLINE+ION'>CHT</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></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=8ubw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ubw OCA], [https://pdbe.org/8ubw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ubw RCSB], [https://www.ebi.ac.uk/pdbsum/8ubw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ubw ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FLVC1_HUMAN FLVC1_HUMAN] Posterior column ataxia-retinitis pigmentosa syndrome. The disease is caused by variants affecting the gene represented in this entry. Defective neuronal heme transmembrane export due to FLVCR1 mutations may abrogate the neuroprotective effects of neuroglobin and initiate an apoptotic cascade that results in the selective degeneration of photoreceptors in the neurosensory retina and sensory neurons in the posterior spinal cord.  Defects in FLVCR1 are a cause of a sensory neuropathy resulting in pain insensitivity. Patients have decreased sensing of pain, temperature and touch. Self-injury, ulcers and amputations are commonly observed in affected individuals.<ref>PMID:27923065</ref> 
== Function ==
[https://www.uniprot.org/uniprot/FLVC1_HUMAN FLVC1_HUMAN] Heme b transporter that mediates heme efflux from the cytoplasm to the extracellular compartment. Heme export depends on the presence of HPX and is required to maintain intracellular free heme balance, protecting cells from heme toxicity. Heme export provides protection from heme or ferrous iron toxicities in liver, brain, sensory neurons and during erythropoiesis, a process in which heme synthesis intensifies. Possibly export coproporphyrin and protoporphyrin IX, which are both intermediate products in the heme biosynthetic pathway. Does not export bilirubin. The molecular mechanism of heme transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated.<ref>PMID:15369674</ref> <ref>PMID:20610401</ref> <ref>PMID:23187127</ref> <ref>PMID:27923065</ref>   (Microbial infection) Confers susceptibility to feline leukemia virus subgroup C (FeLV-C) infection in vitro.<ref>PMID:10400745</ref>   Heme b transporter that promotes heme efflux from the mitochondrion to the cytoplasm. Essential for erythroid differentiation.<ref>PMID:23187127</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Phosphatidylcholine and phosphatidylethanolamine, the two most abundant phospholipids in mammalian cells, are synthesized de novo by the Kennedy pathway from choline and ethanolamine, respectively(1-6). Despite the essential roles of these lipids, the mechanisms that enable the cellular uptake of choline and ethanolamine remain unknown. Here we show that the protein encoded by FLVCR1, whose mutation leads to the neurodegenerative syndrome posterior column ataxia and retinitis pigmentosa(7-9), transports extracellular choline and ethanolamine into cells for phosphorylation by downstream kinases to initiate the Kennedy pathway. Structures of FLVCR1 in the presence of choline and ethanolamine reveal that both metabolites bind to a common binding site comprising aromatic and polar residues. Despite binding to a common site, FLVCR1 interacts in different ways with the larger quaternary amine of choline in and with the primary amine of ethanolamine. Structure-guided mutagenesis identified residues that are crucial for the transport of ethanolamine, but dispensable for choline transport, enabling functional separation of the entry points into the two branches of the Kennedy pathway. Altogether, these studies reveal how FLVCR1 is a high-affinity metabolite transporter that serves as the common origin for phospholipid biosynthesis by two branches of the Kennedy pathway.

Structural basis of lipid head group entry to the Kennedy pathway by FLVCR1.,Son Y, Kenny TC, Khan A, Birsoy K, Hite RK Nature. 2024 May;629(8012):710-716. doi: 10.1038/s41586-024-07374-4. Epub 2024 , May 1. PMID:38693265<ref>PMID:38693265</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8ubw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hite RK]]
[[Category: Son Y]]