Document Detail


Carrier subunit of plasma membrane transporter is required for oxidative folding of its helper subunit.
MedLine Citation:
PMID:  22493502     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We study the amino acid transport system b(0,+) as a model for folding, assembly, and early traffic of membrane protein complexes. System b(0,+) is made of two disulfide-linked membrane subunits: the carrier, b(0,+) amino acid transporter (b(0,+)AT), a polytopic protein, and the helper, related to b(0,+) amino acid transporter (rBAT), a type II glycoprotein. rBAT ectodomain mutants display folding/trafficking defects that lead to type I cystinuria. Here we show that, in the presence of b(0,+)AT, three disulfides were formed in the rBAT ectodomain. Disulfides Cys-242-Cys-273 and Cys-571-Cys-666 were essential for biogenesis. Cys-673-Cys-685 was dispensable, but the single mutants C673S, and C685S showed compromised stability and trafficking. Cys-242-Cys-273 likely was the first disulfide to form, and unpaired Cys-242 or Cys-273 disrupted oxidative folding. Strikingly, unassembled rBAT was found as an ensemble of different redox species, mainly monomeric. The ensemble did not change upon inhibition of rBAT degradation. Overall, these results indicated a b(0,+)AT-dependent oxidative folding of the rBAT ectodomain, with the initial and probably cotranslational formation of Cys-242-Cys-273, followed by the oxidation of Cys-571-Cys-666 and Cys-673-Cys-685, that was completed posttranslationally.
Authors:
Mònica Rius; Josep Chillarón
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-09
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-28     Completed Date:  2012-08-15     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  18190-200     Citation Subset:  IM    
Affiliation:
Department of Physiology and Immunology, Faculty of Biology, University of Barcelona, E-08028 Barcelona, Spain.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Catalytic Domain
Cell Line
DNA Primers
Dogs
Electrophoresis, Gel, Pulsed-Field
Humans
Membrane Transport Proteins / chemistry,  metabolism*
Models, Molecular
Oxidation-Reduction
Protein Folding*
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Membrane Transport Proteins
Comments/Corrections

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