9ba1: Difference between revisions
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The entry | ==Solution NMR structure of the human LETM1 F-EF-hand domain in the presence of calcium== | ||
<StructureSection load='9ba1' size='340' side='right'caption='[[9ba1]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9ba1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9BA1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9BA1 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 10 models</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=9ba1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ba1 OCA], [https://pdbe.org/9ba1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ba1 RCSB], [https://www.ebi.ac.uk/pdbsum/9ba1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ba1 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/LETM1_HUMAN LETM1_HUMAN] Wolf-Hirschhorn syndrome. The disease is caused by variants affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LETM1_HUMAN LETM1_HUMAN] Plays an important role in maintenance of mitochondrial morphology and in mediating either calcium or potassium/proton antiport (PubMed:18628306, PubMed:19797662, PubMed:24344246, PubMed:24898248, PubMed:29123128, PubMed:32139798, PubMed:36055214, PubMed:36321428). Mediates proton-dependent calcium efflux from mitochondrion (PubMed:19797662, PubMed:24344246, PubMed:29123128). Functions also as an electroneutral mitochondrial proton/potassium exchanger (PubMed:24898248, PubMed:36055214, PubMed:36321428). Crucial for the maintenance of mitochondrial tubular networks and for the assembly of the supercomplexes of the respiratory chain (PubMed:18628306, PubMed:36055214). Required for the maintenance of the tubular shape and cristae organization (PubMed:18628306, PubMed:32139798).<ref>PMID:18628306</ref> <ref>PMID:19797662</ref> <ref>PMID:24344246</ref> <ref>PMID:24898248</ref> <ref>PMID:29123128</ref> <ref>PMID:32139798</ref> <ref>PMID:36055214</ref> <ref>PMID:36321428</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
AlphaFold can accurately predict static protein structures but does not account for solvent conditions. Human leucine zipper EF-hand transmembrane protein-1 (LETM1) has one sequence-identifiable EF-hand but how calcium (Ca(2+)) affects structure and function remains enigmatic. Here, we used highly confident AlphaFold Calpha predictions to guide nuclear Overhauser effect (NOE) assignments and structure calculation of the LETM1 EF-hand in the presence of Ca(2+). The resultant NMR structure exposes pairing between a partial loop-helix and full helix-loop-helix, forming an unprecedented F-EF-hand with non-canonical Ca(2+) coordination but enhanced hydrophobicity for protein interactions compared to calmodulin. The structure also reveals the basis for pH sensing at the link between canonical and partial EF-hands. Functionally, mutations that augmented or weakened Ca(2+) binding increased or decreased matrix Ca(2+), respectively, establishing F-EF as a two-way mitochondrial Ca(2+) regulator. Thus, we show how to synergize AI prediction with NMR data, elucidating a solution-specific and extraordinary LETM1 F-EF-hand. | |||
An AI-informed NMR structure reveals an extraordinary LETM1 F-EF-hand domain that functions as a two-way regulator of mitochondrial calcium.,Lin QT, Colussi DM, Lake T, Stathopulos PB Structure. 2024 Sep 17:S0969-2126(24)00363-0. doi: 10.1016/j.str.2024.08.020. PMID:39317198<ref>PMID:39317198</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9ba1" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Lin QT]] | |||
[[Category: Stathopulos PB]] | |||