3LPQ

Human MitoNEET with 2Fe-2S Coordinating Ligand His 87 Replaced With Cys

Summary for 3LPQ

• Entry DOI: 10.2210/pdb3lpq/pdb
• Descriptor: CDGSH iron sulfur domain-containing protein 1, FE2/S2 (INORGANIC) CLUSTER (3 entities in total)
• Functional Keywords: cdgsh protein fold, 2fe-2s cluster, neet fold, homodimer, 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: 18803.02

Authors

Conlan, A.R.,Homer, C.,Axelrod, H.L.,Cohen, A.E.,Abresch, E.C.,Zuris, J.,Nechushtai, R.,Paddock, M.L.,Jennings, P.A. (deposition date: 2010-02-05, release date: 2011-06-01, Last modification date: 2024-02-21)

Primary citation

Conlan, A.R.,Paddock, M.L.,Homer, C.,Axelrod, H.L.,Cohen, A.E.,Abresch, E.C.,Zuris, J.A.,Nechushtai, R.,Jennings, P.A.
Mutation of the His ligand in mitoNEET stabilizes the 2Fe-2S cluster despite conformational heterogeneity in the ligand environment.
Acta Crystallogr.,Sect.D, 67:516-523, 2011

PubMed Abstract: MitoNEET is the only identified Fe-S protein localized to the outer mitochondrial membrane and a 1.5 Å resolution X-ray analysis has revealed a unique structure [Paddock et al. (2007), Proc. Natl Acad. Sci. USA, 104, 14342-14347]. The 2Fe-2S cluster is bound with a 3Cys-1His coordination which defines a new class of 2Fe-2S proteins. The hallmark feature of this class is the single noncysteine ligand His87, which when replaced by Cys decreases the redox potential (E(m)) by ∼300 mV and increases the stability of the cluster by around sixfold. Unexpectedly, the pH dependence of the lifetime of the 2Fe-2S cluster remains the same as in the wild-type protein. Here, the crystal structure of H87C mitoNEET was determined to 1.7 Å resolution (R factor = 18%) to investigate the structural basis of the changes in the properties of the 2Fe-2S cluster. In comparison to the wild type, structural changes are localized to the immediate vicinity of the cluster-binding region. Despite the increased stability, Cys87 displays two distinct conformations, with distances of 2.3 and 3.2 Å between the S(γ) and the outer Fe of the 2Fe-2S cluster. In addition, Lys55 exhibits multiple conformations in the H87C mutant protein. The structure and distinct characteristics of the H87C mutant provide a framework for further studies investigating the effects of mutation on the properties of the 2Fe-2S cluster in this new class of proteins.

PubMed: 21636891
DOI: 10.1107/S0907444911011577

Experimental method

X-RAY DIFFRACTION (1.7 Å)