8rmf: Difference between revisions
New page: '''Unreleased structure''' The entry 8rmf is ON HOLD Authors: Description: Category: Unreleased Structures |
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The entry | ==Structure of the core ISC complex under turnover conditions (FDX2-bound in proximal conformation)== | ||
<StructureSection load='8rmf' size='340' side='right'caption='[[8rmf]], [[Resolution|resolution]] 2.33Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8rmf]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_BL21(DE3) Escherichia coli BL21(DE3)] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8RMF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8RMF 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]] 2.33Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8Q1:S-[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alanyl}amino)ethyl]+dodecanethioate'>8Q1</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</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=8rmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8rmf OCA], [https://pdbe.org/8rmf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8rmf RCSB], [https://www.ebi.ac.uk/pdbsum/8rmf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8rmf ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/LYRM4_HUMAN LYRM4_HUMAN] Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LYRM4_HUMAN LYRM4_HUMAN] Required for nuclear and mitochondrial iron-sulfur protein biosynthesis.<ref>PMID:17331979</ref> <ref>PMID:19454487</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Iron-sulfur (FeS) protein biogenesis in eukaryotes begins with the de novo assembly of [2Fe-2S] clusters by the mitochondrial core iron-sulfur cluster assembly (ISC) complex. This complex comprises the scaffold protein ISCU2, the cysteine desulfurase subcomplex NFS1-ISD11-ACP1, the allosteric activator frataxin (FXN) and the electron donor ferredoxin-2 (FDX2). The structural interaction of FDX2 with the complex remains unclear. Here, we present cryo-EM structures of the human FDX2-bound core ISC complex showing that FDX2 and FXN compete for overlapping binding sites. FDX2 binds in either a 'distal' conformation, where its helix F interacts electrostatically with an arginine patch of NFS1, or a 'proximal' conformation, where this interaction tightens and the FDX2-specific C terminus binds to NFS1, facilitating the movement of the [2Fe-2S] cluster of FDX2 closer to the ISCU2 FeS cluster assembly site for rapid electron transfer. Structure-based mutational studies verify the contact areas of FDX2 within the core ISC complex. | |||
Two-stage binding of mitochondrial ferredoxin-2 to the core iron-sulfur cluster assembly complex.,Steinhilper R, Boss L, Freibert SA, Schulz V, Krapoth N, Kaltwasser S, Lill R, Murphy BJ Nat Commun. 2024 Dec 4;15(1):10559. doi: 10.1038/s41467-024-54585-4. PMID:39632806<ref>PMID:39632806</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8rmf" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Murphy BJ]] | |||
[[Category: Steinhilper R]] | |||
Latest revision as of 09:24, 18 December 2024
Structure of the core ISC complex under turnover conditions (FDX2-bound in proximal conformation)Structure of the core ISC complex under turnover conditions (FDX2-bound in proximal conformation)
Structural highlights
DiseaseLYRM4_HUMAN Severe neonatal lactic acidosis due to NFS1-ISD11 complex deficiency. The disease is caused by mutations affecting the gene represented in this entry. FunctionLYRM4_HUMAN Required for nuclear and mitochondrial iron-sulfur protein biosynthesis.[1] [2] Publication Abstract from PubMedIron-sulfur (FeS) protein biogenesis in eukaryotes begins with the de novo assembly of [2Fe-2S] clusters by the mitochondrial core iron-sulfur cluster assembly (ISC) complex. This complex comprises the scaffold protein ISCU2, the cysteine desulfurase subcomplex NFS1-ISD11-ACP1, the allosteric activator frataxin (FXN) and the electron donor ferredoxin-2 (FDX2). The structural interaction of FDX2 with the complex remains unclear. Here, we present cryo-EM structures of the human FDX2-bound core ISC complex showing that FDX2 and FXN compete for overlapping binding sites. FDX2 binds in either a 'distal' conformation, where its helix F interacts electrostatically with an arginine patch of NFS1, or a 'proximal' conformation, where this interaction tightens and the FDX2-specific C terminus binds to NFS1, facilitating the movement of the [2Fe-2S] cluster of FDX2 closer to the ISCU2 FeS cluster assembly site for rapid electron transfer. Structure-based mutational studies verify the contact areas of FDX2 within the core ISC complex. Two-stage binding of mitochondrial ferredoxin-2 to the core iron-sulfur cluster assembly complex.,Steinhilper R, Boss L, Freibert SA, Schulz V, Krapoth N, Kaltwasser S, Lill R, Murphy BJ Nat Commun. 2024 Dec 4;15(1):10559. doi: 10.1038/s41467-024-54585-4. PMID:39632806[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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