2zxt: Difference between revisions
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The | ==Crystal structure of Tim40/MIA40, a disulfide relay system in mitochondria, solved as MBP fusion protein== | ||
<StructureSection load='2zxt' size='340' side='right'caption='[[2zxt]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2zxt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12], [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZXT FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</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=2zxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zxt OCA], [https://pdbe.org/2zxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zxt RCSB], [https://www.ebi.ac.uk/pdbsum/2zxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zxt ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.[https://www.uniprot.org/uniprot/MIA40_YEAST MIA40_YEAST] Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS). Forms a redox cycle with ERV1 that involves a disulfide relay system. Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria. The oxidized form of MIA40 forms a transient intermolecular disulfide bridge with the reduced precursor protein, resulting in oxidation of the precursor protein that now contains an intramolecular disulfide bond and is able to undergo folding in the IMS. Reduced MIA40 is reoxidized by FAD-linked sulfhydryl oxidase ERV1.<ref>PMID:15359280</ref> <ref>PMID:15364952</ref> <ref>PMID:15620710</ref> <ref>PMID:15989955</ref> <ref>PMID:16181637</ref> <ref>PMID:19667201</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zx/2zxt_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2zxt ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The mitochondrial intermembrane space (IMS) contains many small cysteine-bearing proteins, and their passage across the outer membrane and subsequent folding require recognition and disulfide bond transfer by an oxidative translocator Tim40/Mia40 in the inner membrane facing the IMS. Here we determined the crystal structure of the core domain of yeast Mia40 (Mia40C4) as a fusion protein with maltose-binding protein at a resolution of 3 A. The overall structure of Mia40C4 is a fruit-dish-like shape with a hydrophobic concave region, which accommodates a linker segment of the fusion protein in a helical conformation, likely mimicking a bound substrate. Replacement of the hydrophobic residues in this region resulted in growth defects and impaired assembly of a substrate protein. The Cys296-Cys298 disulfide bond is close to the hydrophobic concave region or possible substrate-binding site, so that it can mediate disulfide bond transfer to substrate proteins. These results are consistent with the growth phenotypes of Mia40 mutant cells containing Ser replacement of the conserved cysteine residues. | |||
Structural basis of yeast Tim40/Mia40 as an oxidative translocator in the mitochondrial intermembrane space.,Kawano S, Yamano K, Naoe M, Momose T, Terao K, Nishikawa S, Watanabe N, Endo T Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14403-7. Epub 2009 Aug 10. PMID:19667201<ref>PMID:19667201</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2zxt" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli K-12]] | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae S288C]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Endo T]] | |||
[[Category: Kawano S]] | |||
[[Category: Momose T]] | |||
[[Category: Watanabe N]] | |||
Latest revision as of 12:40, 6 November 2024
Crystal structure of Tim40/MIA40, a disulfide relay system in mitochondria, solved as MBP fusion proteinCrystal structure of Tim40/MIA40, a disulfide relay system in mitochondria, solved as MBP fusion protein
Structural highlights
FunctionMALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.MIA40_YEAST Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS). Forms a redox cycle with ERV1 that involves a disulfide relay system. Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria. The oxidized form of MIA40 forms a transient intermolecular disulfide bridge with the reduced precursor protein, resulting in oxidation of the precursor protein that now contains an intramolecular disulfide bond and is able to undergo folding in the IMS. Reduced MIA40 is reoxidized by FAD-linked sulfhydryl oxidase ERV1.[1] [2] [3] [4] [5] [6] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe mitochondrial intermembrane space (IMS) contains many small cysteine-bearing proteins, and their passage across the outer membrane and subsequent folding require recognition and disulfide bond transfer by an oxidative translocator Tim40/Mia40 in the inner membrane facing the IMS. Here we determined the crystal structure of the core domain of yeast Mia40 (Mia40C4) as a fusion protein with maltose-binding protein at a resolution of 3 A. The overall structure of Mia40C4 is a fruit-dish-like shape with a hydrophobic concave region, which accommodates a linker segment of the fusion protein in a helical conformation, likely mimicking a bound substrate. Replacement of the hydrophobic residues in this region resulted in growth defects and impaired assembly of a substrate protein. The Cys296-Cys298 disulfide bond is close to the hydrophobic concave region or possible substrate-binding site, so that it can mediate disulfide bond transfer to substrate proteins. These results are consistent with the growth phenotypes of Mia40 mutant cells containing Ser replacement of the conserved cysteine residues. Structural basis of yeast Tim40/Mia40 as an oxidative translocator in the mitochondrial intermembrane space.,Kawano S, Yamano K, Naoe M, Momose T, Terao K, Nishikawa S, Watanabe N, Endo T Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14403-7. Epub 2009 Aug 10. PMID:19667201[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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