View source for 8hik


==The TPP-bound BRIL-SLC19A1/Fab/Nb ternary complex==
<StructureSection load='8hik' size='340' side='right'caption='[[8hik]], [[Resolution|resolution]] 3.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8hik]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8HIK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HIK 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]] 3.72&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</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=8hik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hik OCA], [https://pdbe.org/8hik PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hik RCSB], [https://www.ebi.ac.uk/pdbsum/8hik PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hik ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/S19A1_HUMAN S19A1_HUMAN] The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/S19A1_HUMAN S19A1_HUMAN] Antiporter that mediates the import of reduced folates or a subset of cyclic dinucleotides, driven by the export of organic anions (PubMed:10787414, PubMed:15337749, PubMed:16115875, PubMed:22554803, PubMed:31126740, PubMed:31511694, PubMed:32276275, PubMed:7826387, PubMed:9041240). Mechanistically, acts as a secondary active transporter, which exports intracellular organic anions down their concentration gradients to facilitate the uptake of its substrates (PubMed:22554803, PubMed:31126740, PubMed:31511694). Has high affinity for N5-methyltetrahydrofolate, the predominant circulating form of folate (PubMed:10787414, PubMed:14609557, PubMed:22554803). Also able to mediate the import of antifolate drug methotrexate (PubMed:22554803, PubMed:7615551, PubMed:7641195, PubMed:9767079). Also acts as an importer of immunoreactive cyclic dinucleotides, such as cyclic GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol, and its linkage isomer 3'-3'-cGAMP, thus playing a role in triggering larger immune responses (PubMed:31126740, PubMed:31511694, PubMed:36745868). 5-amino-4-imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR monophosphate, can serve as an organic anion for antiporter activity (PubMed:22554803).<ref>PMID:10787414</ref> <ref>PMID:14609557</ref> <ref>PMID:15337749</ref> <ref>PMID:16115875</ref> <ref>PMID:22554803</ref> <ref>PMID:31126740</ref> <ref>PMID:31511694</ref> <ref>PMID:32276275</ref> <ref>PMID:36745868</ref> <ref>PMID:7615551</ref> <ref>PMID:7641195</ref> <ref>PMID:7826387</ref> <ref>PMID:9041240</ref> <ref>PMID:9767079</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Folate (vitamin B(9)) is the coenzyme involved in one-carbon transfer biochemical reactions essential for cell survival and proliferation, with its inadequacy causing developmental defects or severe diseases. Notably, mammalian cells lack the ability to de novo synthesize folate but instead rely on its intake from extracellular sources via specific transporters or receptors, among which SLC19A1 is the ubiquitously expressed one in tissues. However, the mechanism of substrate recognition by SLC19A1 remains unclear. Here we report the cryo-EM structures of human SLC19A1 and its complex with 5-methyltetrahydrofolate at 3.5-3.6 A resolution and elucidate the critical residues for substrate recognition. In particular, we reveal that two variant residues among SLC19 subfamily members designate the specificity for folate. Moreover, we identify intracellular thiamine pyrophosphate as the favorite coupled substrate for folate transport by SLC19A1. Together, this work establishes the molecular basis of substrate recognition by this central folate transporter.

Molecular mechanism of substrate recognition by folate transporter SLC19A1.,Dang Y, Zhou D, Du X, Zhao H, Lee CH, Yang J, Wang Y, Qin C, Guo Z, Zhang Z Cell Discov. 2022 Dec 28;8(1):141. doi: 10.1038/s41421-022-00508-w. PMID:36575193<ref>PMID:36575193</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8hik" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Dang Y]]
[[Category: Zhang Z]]