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Titolo:
Functional role of critical stripe residues in transmembrane span 7 of theserotonin transporter - Effects of Na+, Li+, and methanethiosulfonate reagents
Autore:
Kamdar, G; Penado, KMY; Rudnick, G; Stephan, MM;
Indirizzi:
Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA Yale Univ NewHaven CT USA 06510 Dept Pharmacol, New Haven, CT 06510 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 6, volume: 276, anno: 2001,
pagine: 4038 - 4045
SICI:
0021-9258(20010209)276:6<4038:FROCSR>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN DOPAMINE TRANSPORTER; EXPRESSION SYSTEM; COCAINE BINDING; AMINO-ACID; DOMAIN; MUTATIONS; SUBSTRATE; SITE; NOREPINEPHRINE; ACCESSIBILITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Stephan, MM Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06510 USA Yale Univ 333 Cedar St New Haven CT USA 06510 en, CT 06510 USA
Citazione:
G. Kamdar et al., "Functional role of critical stripe residues in transmembrane span 7 of theserotonin transporter - Effects of Na+, Li+, and methanethiosulfonate reagents", J BIOL CHEM, 276(6), 2001, pp. 4038-4045

Abstract

Mutations at critical residue positions in transmembrane span 7 (TM7) of the serotonin transporter affect the Na+ dependence of transport. It was possible that these residues, which form a stripe along one side of the predicted alpha -helix. formed part of a water-filled pore for Na+. We tested whether cysteine substitutions in TM7 mere accessible to hydrophilic, membrane-impermeant methanethiosulfonate (MTS) reagents. Although all five cysteine-containing mutants tested were sensitive to these reagents, noncysteine control mutants at the same positions were in most cases equally sensitive. In all cases, MTS sensitivity could be traced to changes in accessibility ofa native cysteine residue in extracellular loop 1, Cys-109. Moreover, noneof the TM7 cysteines reacted with the biotinylating reagent MTSEA-biotin when tested in the C109A background. It is thus unlikely that the critical stripe forms part of a water-filled pore. Instead, studies of the ion dependence of the reaction between Cys-109 and MTS reagents lead to the conclusion that TM7 is involved in propagating conformational changes caused by ion binding, perhaps as part of the translocation mechanism. The critical stripe residues on TM7 probably represent a close contact region between TM7 andone or more other TMs in the transporter's three-dimensional structure.

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Documento generato il 10/07/20 alle ore 18:41:04