Direct evidence that the N-terminal extensions of the TAP complex act as autonomous interaction scaffolds for the assembly of the MHC I peptide-loading complex
- The loading of antigenic peptides onto major histocompatibility complex class I (MHC I) molecules is an essential step in the adaptive immune response against virally or malignantly transformed cells. The ER-resident peptide-loading complex (PLC) consists of the transporter associated with antigen processing (TAP1 and TAP2), assembled with the auxiliary factors tapasin and MHC I. Here, we demonstrated that the N-terminal extension of each TAP subunit represents an autonomous domain, named TMD0, which is correctly targeted to and inserted into the ER membrane. In the absence of coreTAP, each TMD0 recruits tapasin in a 1:1 stoichiometry. Although the TMD0s lack known ER retention/retrieval signals, they are localized to the ER membrane even in tapasin-deficient cells. We conclude that the TMD0s of TAP form autonomous interaction hubs linking antigen translocation into the ER with peptide loading onto MHC I, hence ensuring a major function in the integrity of the antigen-processing machinery.
Author: | Sabine Hulpke, Maiko Tomioka, Elisabeth Kremmer, Kazumitsu UedaORCiD, Rupert AbeleORCiDGND, Robert TampéORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-288735 |
DOI: | https://doi.org/10.1007/s00018-012-1005-6 |
ISSN: | 1420-9071 |
ISSN: | 1420-682X |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/22638925 |
Parent Title (English): | Cellular and molecular life sciences : (CMLS) |
Publisher: | Springer |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2012/05/27 |
Date of first Publication: | 2012/05/27 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2013/02/14 |
Volume: | 69 |
Page Number: | 11 |
First Page: | 3317 |
Last Page: | 3327 |
Note: | Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
HeBIS-PPN: | 331500736 |
Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Sammlung Biologie / Sondersammelgebiets-Volltexte | |
Licence (German): | Creative Commons - Namensnennung 3.0 |