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2k3j

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Revision as of 06:54, 19 February 2020

The solution structure of human Mia40

Structural highlights

2k3j is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	CHCHD4, MIA40 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MIA40_HUMAN] Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17. Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS). Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria. The oxidized form of CHCHD4/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 CHCHD4/MIA40 is then reoxidized by GFER/ERV1 via a disulfide relay system.^[1] ^[2] ^[3] ^[4]

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 PubMed

MIA40 has a key role in oxidative protein folding in the mitochondrial intermembrane space. We present the solution structure of human MIA40 and its mechanism as a catalyst of oxidative folding. MIA40 has a 66-residue folded domain made of an alpha-helical hairpin core stabilized by two structural disulfides and a rigid N-terminal lid, with a characteristic CPC motif that can donate its disulfide bond to substrates. The CPC active site is solvent-accessible and sits adjacent to a hydrophobic cleft. Its second cysteine (Cys55) is essential in vivo and is crucial for mixed disulfide formation with the substrate. The hydrophobic cleft functions as a substrate binding domain, and mutations of this domain are lethal in vivo and abrogate binding in vitro. MIA40 represents a thioredoxin-unrelated, minimal oxidoreductase, with a facile CPC redox active site that ensures its catalytic function in oxidative folding in mitochondria.

MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria.,Banci L, Bertini I, Cefaro C, Ciofi-Baffoni S, Gallo A, Martinelli M, Sideris DP, Katrakili N, Tokatlidis K Nat Struct Mol Biol. 2009 Feb;16(2):198-206. Epub 2009 Feb 1. PMID:19182799^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hofmann S, Rothbauer U, Muhlenbein N, Baiker K, Hell K, Bauer MF. Functional and mutational characterization of human MIA40 acting during import into the mitochondrial intermembrane space. J Mol Biol. 2005 Oct 28;353(3):517-28. PMID:16185709 doi:http://dx.doi.org/S0022-2836(05)01031-4
↑ Sztolsztener ME, Brewinska A, Guiard B, Chacinska A. Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40. Traffic. 2013 Mar;14(3):309-20. doi: 10.1111/tra.12030. Epub 2012 Dec 16. PMID:23186364 doi:http://dx.doi.org/10.1111/tra.12030
↑ Banci L, Bertini I, Cefaro C, Ciofi-Baffoni S, Gallo A, Martinelli M, Sideris DP, Katrakili N, Tokatlidis K. MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria. Nat Struct Mol Biol. 2009 Feb;16(2):198-206. Epub 2009 Feb 1. PMID:19182799 doi:10.1038/nsmb.1553
↑ Banci L, Bertini I, Cefaro C, Cenacchi L, Ciofi-Baffoni S, Felli IC, Gallo A, Gonnelli L, Luchinat E, Sideris D, Tokatlidis K. Molecular chaperone function of Mia40 triggers consecutive induced folding steps of the substrate in mitochondrial protein import. Proc Natl Acad Sci U S A. 2010 Nov 8. PMID:21059946 doi:10.1073/pnas.1010095107
↑ Banci L, Bertini I, Cefaro C, Ciofi-Baffoni S, Gallo A, Martinelli M, Sideris DP, Katrakili N, Tokatlidis K. MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria. Nat Struct Mol Biol. 2009 Feb;16(2):198-206. Epub 2009 Feb 1. PMID:19182799 doi:10.1038/nsmb.1553

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2k3j"

@@ Line 1: / Line 1: @@
 ==The solution structure of human Mia40==
-<StructureSection load='2k3j' size='340' side='right' caption='[[2k3j]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='2k3j' size='340' side='right'caption='[[2k3j]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2k3j]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K3J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K3J FirstGlance]. <br>
@@ Line 33: / Line 33: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Baffoni, S Ciofi]]
 [[Category: Bertini, I]]

2k3j

From Proteopedia

Revision as of 06:54, 19 February 2020

The solution structure of human Mia40

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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