Linked Life Data

19011240

Source:http://linkedlifedata.com/resource/pubmed/id/19011240

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-1-12
pubmed:abstractText
Oxidative folding drives the import of proteins containing twin CXnC motifs into the intermembrane space of mitochondria. This import pathway employs a disulfide relay system whose key components are the redox-regulated import receptor Mia40 and the thiol oxidase Erv1. Mia40 contains six cysteine residues in a CPC-CX9C-CX9C arrangement in a highly conserved domain. We show that this domain is sufficient for the function of Mia40. By analysis of Mia40 cysteine mutants we demonstrate that the cysteine residues have distinct roles and are not equally important for Mia40 function. The second cysteine residue is essential for viability of yeast cells. It is required for the interaction of Mia40 with Erv1 in a disulfide intermediate and forms a redox-sensitive disulfide bond with the first cysteine residue. Both cysteine residues are required for the oxidation of the substrate, Tim10, in a reconstituted system comprised of Mia40 and Erv1. Mutants with amino acid exchanges in the third and sixth cysteine residues have severe defects in growth and in the import of intermembrane space proteins. These Mia40 variants are not tightly folded. We conclude that the cysteine residues of the twin CX9C motif have a structural role and stabilize Mia40. In particular, the disulfide bond formed by the third and sixth cysteine residues apparently supports a conformation crucial for the function of Mia40. Furthermore, the disulfide bond in the CPC segment mediates the redox reactions with the thiol oxidase Erv1 and substrate proteins in mitochondria.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1353-63
pubmed:dateRevised
2009-5-15
pubmed:meshHeading
pubmed-meshheading:19011240-Amino Acid Motifs, pubmed-meshheading:19011240-Amino Acid Substitution, pubmed-meshheading:19011240-Cysteine, pubmed-meshheading:19011240-Disulfides, pubmed-meshheading:19011240-Membrane Proteins, pubmed-meshheading:19011240-Mitochondria, pubmed-meshheading:19011240-Mitochondrial Membrane Transport Proteins, pubmed-meshheading:19011240-Mitochondrial Proteins, pubmed-meshheading:19011240-Mutation, pubmed-meshheading:19011240-Oxidation-Reduction, pubmed-meshheading:19011240-Oxidoreductases Acting on Sulfur Group Donors, pubmed-meshheading:19011240-Protein Folding, pubmed-meshheading:19011240-Protein Structure, Tertiary, pubmed-meshheading:19011240-Protein Transport, pubmed-meshheading:19011240-Saccharomyces cerevisiae, pubmed-meshheading:19011240-Saccharomyces cerevisiae Proteins
pubmed:year
2009
pubmed:articleTitle
Structural and functional roles of the conserved cysteine residues of the redox-regulated import receptor Mia40 in the intermembrane space of mitochondria.
pubmed:affiliation
Adolf Butenandt Institut für Physiologische Chemie, Ludwig-Maximilians-Universität München, Butenandtstrasse 5, 81377 München, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't