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Proc Natl Acad Sci U S A


Title:Evidence for peptide transport across microsomal membranes
Author(s):Koppelman B; Zimmerman DL; Walter P; Brodsky FM;
Address:"Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0446"
Journal Title:Proc Natl Acad Sci U S A
Year:1992
Volume:89
Issue:9
Page Number:3908 - 3912
DOI: 10.1073/pnas.89.9.3908
ISSN/ISBN:0027-8424 (Print) 1091-6490 (Electronic) 0027-8424 (Linking)
Abstract:"Antigenic peptides bound to class I molecules of the major histocompatibility complex (MHC) are recognized by T-cell receptors during development of an antiviral immune response. T cells respond to peptides derived from cytoplasmic viral proteins as well as viral membrane proteins, indicating that a pathway exists for the transport of proteins or peptides from the cytosol into the compartment(s) where the MHC class I molecules assemble. To investigate this pathway, we have developed an in vitro assay for the transport of peptides into microsomal vesicles. This assay provides evidence for the transport of chemically synthesized peptides (13-21 amino acids) containing N-linked glycosylation acceptor sequences, which serve as glycosylation substrates. Their transport results in depletion of the pool of available dolichol high-mannose oligosaccharides in the lumen of the microsomal vesicles. We have observed transport of peptides derived from antigenic human immunodeficiency virus gag and influenza B nucleoprotein sequences, but transport of a third randomly selected peptide was not detected, suggesting specificity of the transport process. We were not able to demonstrate ATP dependence of this peptide transport process by using apyrase and an ATPase inhibitor. This result was unexpected in light of the recent identification of MHC-linked genes with homology to ATP-binding cassette transporters, which have been proposed to mediate peptide transport"
Keywords:Amino Acid Sequence Animals Biological Transport Dogs Endoplasmic Reticulum/metabolism Glycosylation In Vitro Techniques Mating Factor Microsomes/*metabolism Molecular Sequence Data Oligomycins/pharmacology Peptides/chemistry/*metabolism Protein Precursor;
Notes:"MedlineKoppelman, B Zimmerman, D L Walter, P Brodsky, F M eng AR20894/AR/NIAMS NIH HHS/ GM26691/GM/NIGMS NIH HHS/ GM32384/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 1992/05/01 Proc Natl Acad Sci U S A. 1992 May 1; 89(9):3908-12. doi: 10.1073/pnas.89.9.3908"

 
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