Biogenesis of functional antigenic peptide transporter TAP requires assembly of pre-existing TAP1 with newly synthesized TAP2

The Journal of Biological Chemistry
Kirstin KeusekottenMichael R Knittler

Abstract

The transporter associated with antigen processing (TAP) is essential for the delivery of antigenic peptides from the cytosol into the endoplasmic reticulum (ER), where they are loaded onto major histocompatibility complex class I molecules. TAP is a heterodimeric transmembrane protein that comprises the homologous subunits TAP1 and TAP2. As for many other oligomeric protein complexes, which are synthesized in the ER, the process of subunit assembly is essential for TAP to attain a native functional state. Here, we have analyzed the individual requirements of TAP1 and TAP2 for the formation of a functional TAP complex. Unlike TAP1, TAP2 is very unstable when expressed in isolation. We show that heterodimerization of TAP subunits is required for maintaining a stable level of TAP2. By using an in vitro expression system we demonstrate that the biogenesis of functional TAP depends on the assembly of preexisting TAP1 with newly synthesized TAP2, but not vice versa. The pore forming core transmembrane domain (core TMD) of in vitro expressed TAP2 is necessary and sufficient to allow functional complex formation with pre-existing TAP1. We propose that the observed assembly mechanism of TAP protects newly synthesized TAP2 from rapid de...Continue Reading

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Citations

Nov 1, 2007·Journal of Bioenergetics and Biomembranes·Daphne Nikles, Robert Tampé
Sep 2, 2009·Immunology and Cell Biology·Angelo TheodoratosAude M Fahrer
Mar 20, 2009·Proceedings of the National Academy of Sciences of the United States of America·Giani OanceaRobert Tampé
Mar 2, 2011·The Journal of Biological Chemistry·Christian SchölzRobert Tampé
Jul 26, 2012·The Journal of Biological Chemistry·Michaela S PanterPeter Cresswell
May 12, 2009·Biological Chemistry·Christian Schölz, Robert Tampé
Jan 5, 2011·Clinical & Developmental Immunology·Georg EschenburgHolger N Lode
Feb 2, 2008·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Jeroen AerssensBernard Coulie
Sep 8, 2007·Traffic·David StepenskyPeter Cresswell
Jun 19, 2007·Biochimica Et Biophysica Acta·Jean-Pierre GilletJosé Remacle
Apr 14, 2009·Molecular Immunology·Laura C SimoneJoyce C Solheim
May 18, 2017·Expert Opinion on Drug Metabolism & Toxicology·Ela CerovskaPavel Soucek
May 16, 2018·Frontiers in Cell and Developmental Biology·Rupert Abele, Robert Tampé
Feb 7, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ralf M LeonhardtPeter Cresswell
Aug 24, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nathalie VigneronRalf M Leonhardt
May 29, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Anika TabassumTomasz M Karpiński

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