TY  - JOUR
A1  - Herget, Meike
A1  - Oancea, Giani
A1  - Schrodt, Susanne
A1  - Karas, Michael
A1  - Tampé, Robert
A1  - Abele, Rupert
T1  - Mechanism of substrate sensing and signal transmission within an ABC transporter: use of a Trojan horse strategy
T2  - Journal of biological chemistry
N2  - 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.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76309
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-763098
SN  - 0021-9258
VL  - 282.2007
IS  - 6
SP  - 3871
EP  - 3880
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -