Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease
- University of Illinois at Urbana-Champaign, United States
- Universidad de La Rioja, Spain
Abstract
The secretion of peptides and proteins is essential for survival and ecological adaptation of bacteria. Dual-functional ATP-binding cassette transporters export antimicrobial or quorum signaling peptides in Gram-positive bacteria. Their substrates contain a leader sequence that is excised by an N-terminal peptidase C39 domain at a double Gly motif. We characterized the protease domain (LahT150) of a transporter from a lanthipeptide biosynthetic operon in Lachnospiraceae and demonstrate that this protease can remove the leader peptide from a diverse set of peptides. The 2.0 Å resolution crystal structure of the protease domain in complex with a covalently bound leader peptide demonstrates the basis for substrate recognition across the entire class of such transporters. The structural data also provide a model for understanding the role of leader peptide recognition in the translocation cycle, and the function of degenerate, non-functional C39-like domains (CLD) in substrate recruitment in toxin exporters in Gram-negative bacteria.
Data availability
Diffraction data has been deposited at Protein Data Bank under 6MPZ.
Article and author information
Author details
Gonzalo Jiménez-Osés
Wilfred A van der Donk
Funding
National Institutes of Health (GM058822)
- Wilfred A van der Donk
Ministerio de Economía y Competitividad (CTQ2015-70524-R)
- Gonzalo Jiménez-Osés
National Institutes of Health (GM079038)
- Satish K Nair
Ministerio de Economía y Competitividad (RYC-2013-14706)
- Gonzalo Jiménez-Osés
Universidad de La Rioja (Predoctoral fellowship)
- Nuria Mazo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Bobeica et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease
eLife 8:e42305.
https://doi.org/10.7554/eLife.42305
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