| Structural highlights
4f28 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| Related: | 3lpq, 3ew0, 2qh7, 4f1e, 4f2c, 4ezf |
| Gene: | C10orf70, CISD1, MDS029, ZCD1 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[CISD1_HUMAN] Plays a key role in regulating maximal capacity for electron transport and oxidative phosphorylation (By similarity). May be involved in Fe-S cluster shuttling and/or in redox reactions.[1] [2]
Publication Abstract from PubMed
Metalloproteins (MPs) comprise one-third of all known protein structures. This diverse set of proteins contain a plethora of unique inorganic moieties capable of performing chemistry that would otherwise be impossible using only the amino acids found in nature. Most of the well-studied MPs are generally viewed as being very rigid in structure, and it is widely thought that the properties of the metal centers are primarily determined by the small fraction of amino acids that make up the local environment. Here we examine both theoretically and experimentally whether distal regions can influence the metal center in the diabetes drug target mitoNEET. We demonstrate that a loop (L2) 20 A away from the metal center exerts allosteric control over the cluster binding domain and regulates multiple properties of the metal center. Mutagenesis of L2 results in significant shifts in the redox potential of the [2Fe-2S] cluster and orders of magnitude effects on the rate of [2Fe-2S] cluster transfer to an apo-acceptor protein. These surprising effects occur in the absence of any structural changes. An examination of the native basin dynamics of the protein using all-atom simulations shows that twisting in L2 controls scissoring in the cluster binding domain and results in perturbations to one of the cluster-coordinating histidines. These allosteric effects are in agreement with previous folding simulations that predicted L2 could communicate with residues surrounding the metal center. Our findings suggest that long-range dynamical changes in the protein backbone can have a significant effect on the functional properties of MPs.
Allosteric control in a metalloprotein dramatically alters function.,Baxter EL, Zuris JA, Wang C, Vo PL, Axelrod HL, Cohen AE, Paddock ML, Nechushtai R, Onuchic JN, Jennings PA Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):948-53. doi:, 10.1073/pnas.1208286110. Epub 2012 Dec 27. PMID:23271805[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wiley SE, Paddock ML, Abresch EC, Gross L, van der Geer P, Nechushtai R, Murphy AN, Jennings PA, Dixon JE. The outer mitochondrial membrane protein mitoNEET contains a novel redox-active 2Fe-2S cluster. J Biol Chem. 2007 Aug 17;282(33):23745-9. Epub 2007 Jun 21. PMID:17584744 doi:C700107200
- ↑ Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA. MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14342-7. Epub 2007 Aug 31. PMID:17766440
- ↑ Baxter EL, Zuris JA, Wang C, Vo PL, Axelrod HL, Cohen AE, Paddock ML, Nechushtai R, Onuchic JN, Jennings PA. Allosteric control in a metalloprotein dramatically alters function. Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):948-53. doi:, 10.1073/pnas.1208286110. Epub 2012 Dec 27. PMID:23271805 doi:http://dx.doi.org/10.1073/pnas.1208286110
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