Linked Life Data

15568812

Source:http://linkedlifedata.com/resource/pubmed/id/15568812

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
2004-11-30
pubmed:abstractText
To investigate the structural and functional features of the second alpha-helical transmembrane segment (TM2) of the mitochondrial ADP/ATP carrier (AAC), we adopted cysteine scanning mutagenesis analysis. Single-cysteine mutations of yeast AAC were systematically introduced at residues 98-106 in TM2, and the mutants were treated with the fluorescent SH reagent eosin-5-maleimide (EMA). EMA modified different amino acid residues of alpha-helical TM2 between the two distinct carrier conformations, called the m-state and the c-state, in which the substrate recognition site faces the matrix and cytosol, respectively. When amino acids in the helix were projected on a wheel plot, these EMA-modified amino acids were observed at distinct sides of the wheel. Since the SH reagent specifically modified cysteine in the water-accessible environment, these results indicate that distinct helical surfaces of TM2 faced the water-accessible space between the two conformations, possibly as a result of twisting of this helix. In the recently reported crystal structure of bovine AAC, several amino acids faced cocrystallized carboxyatractyloside (CATR), a specific inhibitor of the carrier. These residues correspond to those modified with EMA in the yeast carrier in the c-state. Since the binding site of CATR is known to overlap that of the transport substrate, the water-accessible space was thought to be a substrate transport pathway, and hence, the observed twisting of TM2 between the m-state and the c-state may be involved in the process of substrate translocation. On the basis of the results, the roles of TM2 in the transport function of AAC were discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15204-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15568812-Amino Acid Sequence, pubmed-meshheading:15568812-Amino Acid Substitution, pubmed-meshheading:15568812-Animals, pubmed-meshheading:15568812-Atractyloside, pubmed-meshheading:15568812-Binding Sites, pubmed-meshheading:15568812-Cattle, pubmed-meshheading:15568812-Cysteine, pubmed-meshheading:15568812-Enzyme Inhibitors, pubmed-meshheading:15568812-Eosine Yellowish-(YS), pubmed-meshheading:15568812-Intracellular Membranes, pubmed-meshheading:15568812-Mitochondrial ADP, ATP Translocases, pubmed-meshheading:15568812-Molecular Sequence Data, pubmed-meshheading:15568812-Mutagenesis, Site-Directed, pubmed-meshheading:15568812-Protein Conformation, pubmed-meshheading:15568812-Protein Structure, Secondary, pubmed-meshheading:15568812-Protein Transport, pubmed-meshheading:15568812-Saccharomyces cerevisiae Proteins
pubmed:year
2004
pubmed:articleTitle
Twisting of the second transmembrane alpha-helix of the mitochondrial ADP/ATP carrier during the transition between two carrier conformational states.
pubmed:affiliation
Faculty of Pharmaceutical Sciences, University of Tokushima, Shomachi-1, Tokushima 770-8505, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't