Peptide translocation by the lysosomal ABC transporter TAPL is regulated by coupling efficiency and activation energy
- The lysosomal polypeptide transporter TAPL belongs to the superfamily of ATP-binding cassette transporters. TAPL forms a homodimeric transport complex, which translocates oligo- and polypeptides into the lumen of lysosomes driven by ATP hydrolysis. Although the structure and the function of ABC transporters were intensively studied in the past, details about the single steps of the transport cycle are still elusive. Therefore, we analyzed the coupling of peptide binding, transport and ATP hydrolysis for different substrate sizes. Although longer and shorter peptides bind with the same affinity and are transported with identical Km values, they differ significantly in their transport rates. This difference can be attributed to a higher activation energy for the longer peptide. TAPL shows a basal ATPase activity, which is inhibited in the presence of longer peptides. Uncoupling between ATP hydrolysis and peptide transport increases with peptide length. Remarkably, also the type of nucleotide determines the uncoupling. While GTP is hydrolyzed as good as ATP, peptide transport is significantly reduced. In conclusion, TAPL does not differentiate between transport substrates in the binding process but during the following steps in the transport cycle, whereas, on the other hand, not only the coupling efficiency but also the activation energy varies depending on the size of peptide substrate.
Author: | Christoph BockGND, Tina ZollmannGND, Katharina-Astrid Lindt, Robert TampéORCiDGND, Rupert AbeleORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-507502 |
DOI: | https://doi.org/10.1038/s41598-019-48343-6 |
ISSN: | 2045-2322 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31417173 |
Parent Title (English): | Scientific reports |
Publisher: | Macmillan Publishers Limited, part of Springer Nature |
Place of publication: | [London] |
Document Type: | Article |
Language: | English |
Year of Completion: | 2019 |
Date of first Publication: | 2019/08/15 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2019/08/19 |
Tag: | Enzyme mechanisms; Membrane proteins |
Volume: | 9 |
Issue: | 1, Art. 11884 |
Page Number: | 12 |
First Page: | 1 |
Last Page: | 12 |
Note: | Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
HeBIS-PPN: | 453741169 |
Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
Wissenschaftliche Zentren und koordinierte Programme / Sonderforschungsbereiche / Forschungskollegs | |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |