View source for 9dmr


==Solution NMR structure of the calcium insensitive human LETM1 F-EF-hand domain mutant in the absence of calcium==
<StructureSection load='9dmr' size='340' side='right'caption='[[9dmr]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9dmr]] 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=9DMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DMR 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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9dmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9dmr OCA], [https://pdbe.org/9dmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9dmr RCSB], [https://www.ebi.ac.uk/pdbsum/9dmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9dmr 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 ==
Leucine zipper EF-hand containing transmembrane protein-1 (LETM1) plays a critical role in mitochondrial function, with haploinsufficiency linked to Wolf-Hirschhorn syndrome. Here, we present the solution NMR structure of the calcium (Ca(2+))-depleted LETM1 EF-hand domain, revealing a closed conformation facilitated by a distinct F(1)-helix pivot rather than decreased interhelical angle. Further, we observe regiospecific unfolding in response to hot and cold denaturation and show H662 has a pKa in-line with physiological pH fluctuations. Finally, we demonstrate Ca(2+)-dependent transient interactions between the EF-hand and other LETM1 or GHITM protein domains. Collectively, our data reveal the apo-to-holo structural dynamics and mechanisms underlying the multi-modal sensing by the LETM1 EF-hand domain, highlighting its role as an adaptable regulatory element within the mitochondrial matrix.

The apo LETM1 F-EF-hand adopts a closed conformation that underlies a multi-modal sensory role in mitochondria.,Lin QT, Colussi DM, Stathopulos PB FEBS Lett. 2025 Apr;599(7):971-988. doi: 10.1002/1873-3468.70006. Epub 2025 Feb , 10. PMID:39927520<ref>PMID:39927520</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9dmr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lin QT]]
[[Category: Stathopulos PB]]