Specific lipids modulate the transporter associated with antigen processing (TAP)

  • The transporter associated with antigen processing (TAP) plays a key role in adaptive immunity by translocating proteasomal degradation products from the cytosol into the endoplasmic reticulum lumen for subsequent loading onto major histocompatibility (MHC) class I molecules. For functional and structural analysis of this ATP-binding cassette complex, we established the overexpression of TAP in the methylotrophic yeast Pichia pastoris. Screening of optimal solubilization and purification conditions allowed the isolation of the heterodimeric transport complex, yielding 30 mg of TAP/liter of culture. Detailed analysis of TAP function in the membrane, solubilized, purified, and reconstituted states revealed a direct influence of the native lipid environment on activity. TAP-associated phospholipids, essential for function, were profiled by liquid chromatography Fourier transform mass spectrometry. The antigen translocation activity is stimulated by phosphatidylinositol and -ethanolamine, whereas cholesterol has a negative effect on TAP activity.

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Metadaten
Author:Christian SchölzORCiDGND, David Parcej, Christer Stenby EjsingORCiDGND, Horst RobenekGND, Ina L. UrbatschORCiD, Robert TampéORCiDGND
URN:urn:nbn:de:hebis:30:3-765801
DOI:https://doi.org/https://doi.org/10.1074/jbc.M110.216416
ISSN:0021-9258
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/21357424
Parent Title (English):Journal of biological chemistry
Publisher:American Society for Biochemistry and Molecular Biology Publications
Place of publication:Bethesda, Md
Document Type:Article
Language:English
Date of Publication (online):2021/01/04
Year of first Publication:2011
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2024/02/21
Tag:ABC Transporter; ATPases; Antigen Processing; Peptides; Reconstitution of Membrane Transporters
Volume:286.2011
Issue:15
Page Number:11
First Page:13346
Last Page:13356
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International