3EW0

The novel 2Fe-2S outer mitochondrial protein mitoNEET displays conformational flexibility in its N-terminal cytoplasmic tethering domain

Summary for 3EW0

• Entry DOI: 10.2210/pdb3ew0/pdb
• Related: 2qh7
• Descriptor: CDGSH iron sulfur domain-containing protein 1, FE2/S2 (INORGANIC) CLUSTER (3 entities in total)
• Functional Keywords: mitochondrial outer membrane, 2fe-2s proteins, isotopic labeling, highyield expression, iron, iron-sulfur, membrane, metal-binding, mitochondrion, mitochondrion outer membrane, signal-anchor, transmembrane, metal binding protein
• Biological source: Homo sapiens (Human)
• Cellular location: Mitochondrion outer membrane ; Single- pass type III membrane protein : Q9NZ45
• Total number of polymer chains: 2
• Total formula weight: 18913.05

Authors

Conlan, A.R.,Paddock, M.L.,Wiley, S.,Axelrod, H.L.,Cohen, A.E.,Abresch, E.C.,Roy, M.,Nechushtai, R.,Jennings, P.A. (deposition date: 2008-10-13, release date: 2009-07-07, Last modification date: 2023-09-06)

Primary citation

Conlan, A.R.,Paddock, M.L.,Axelrod, H.L.,Cohen, A.E.,Abresch, E.C.,Wiley, S.,Roy, M.,Nechushtai, R.,Jennings, P.A.
The novel 2Fe-2S outer mitochondrial protein mitoNEET displays conformational flexibility in its N-terminal cytoplasmic tethering domain.
Acta Crystallogr.,Sect.F, 65:654-659, 2009

PubMed Abstract: A primary role for mitochondrial dysfunction is indicated in the pathogenesis of insulin resistance. A widely used drug for the treatment of type 2 diabetes is pioglitazone, a member of the thiazolidinedione class of molecules. MitoNEET, a 2Fe-2S outer mitochondrial membrane protein, binds pioglitazone [Colca et al. (2004), Am. J. Physiol. Endocrinol. Metab. 286, E252-E260]. The soluble domain of the human mitoNEET protein has been expressed C-terminal to the superfolder green fluorescent protein and the mitoNEET protein has been isolated. Comparison of the crystal structure of mitoNEET isolated from cleavage of the fusion protein (1.4 A resolution, R factor = 20.2%) with other solved structures shows that the CDGSH domains are superimposable, indicating proper assembly of mitoNEET. Furthermore, there is considerable flexibility in the position of the cytoplasmic tethering arms, resulting in two different conformations in the crystal structure. This flexibility affords multiple orientations on the outer mitochondrial membrane.

PubMed: 19574633
DOI: 10.1107/S1744309109019605

Experimental method

X-RAY DIFFRACTION (1.4 Å)