Mechanism of substrate sensing and signal transmission within an ABC transporter: use of a Trojan horse strategy
- By translocating proteasomal degradation products into the endoplasmic reticulum for loading of major histocompatibility complex I molecules, the ABC transporter TAP plays a focal role in the adaptive immunity against infected or malignantly transformed cells. A key question regarding the transport mechanism is how the quality of the incoming peptide is detected and how this information is transmitted to the ATPase domains. To identify residues involved in this process, we evolved a Trojan horse strategy in which a small artificial protease is inserted into antigenic epitopes. After binding, the TAP backbone in contact is cleaved, allowing the peptide sensor site to be mapped by mass spectrometry. Within this sensor site, we identified residues that are essential for tight coupling of peptide binding and transport. This sensor and transmission interface is restructured during the ATP hydrolysis cycle, emphasizing its important function in the cross-talk between the transmembrane and the nucleotide-binding domains. This allocrite sensor may be similarly positioned in other members of the ABC exporter family.
Author: | Meike HergetGND, Giani OanceaGND, Susanne SchrodtGND, Michael KarasGND, Robert TampéORCiDGND, Rupert AbeleORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-763098 |
DOI: | https://doi.org/10.1074/jbc.M608480200 |
ISSN: | 0021-9258 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/17164240 |
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: | 2007 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2024/02/21 |
Volume: | 282.2007 |
Issue: | 6 |
Page Number: | 10 |
First Page: | 3871 |
Last Page: | 3880 |
Institutes: | Biochemie, Chemie und Pharmazie |
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): | Creative Commons - CC BY - Namensnennung 4.0 International |