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Title: Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease

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.

Authors:
ORCiD logo [1]; ORCiD logo [2];  [1];  [3]; ORCiD logo [1]; ORCiD logo [4]; ORCiD logo [5]; ORCiD logo [6]
  1. Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, United States
  2. Roger Adams Laboratory, Department of Biochemistry, University of llinois at Urbana-Champaign, Urbana, United States
  3. Departamento de Química, Centro de Investigación en Síntesis Química, Universidad de La Rioja, La Rioja, Spain
  4. Departamento de Química, Centro de Investigación en Síntesis Química, Universidad de La Rioja, La Rioja, Spain; CICbioGUNE, Derio, Spain
  5. Roger Adams Laboratory, Department of Biochemistry, University of llinois at Urbana-Champaign, Urbana, United States; Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, United States
  6. Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, United States; Roger Adams Laboratory, Department of Biochemistry, University of llinois at Urbana-Champaign, Urbana, United States; Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, United States
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
NIHFOREIGN
OSTI Identifier:
1502241
Resource Type:
Journal Article
Journal Name:
eLife
Additional Journal Information:
Journal Volume: 8; Journal Issue: 01, 2019; Journal ID: ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Bobeica, Silvia C., Dong, Shi-Hui, Huo, Liujie, Mazo, Nuria, McLaughlin, Martin I., Jiménez-Osés, Gonzalo, Nair, Satish K., and van der Donk, Wilfred A. Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease. United States: N. p., 2019. Web. doi:10.7554/eLife.42305.
Bobeica, Silvia C., Dong, Shi-Hui, Huo, Liujie, Mazo, Nuria, McLaughlin, Martin I., Jiménez-Osés, Gonzalo, Nair, Satish K., & van der Donk, Wilfred A. Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease. United States. doi:10.7554/eLife.42305.
Bobeica, Silvia C., Dong, Shi-Hui, Huo, Liujie, Mazo, Nuria, McLaughlin, Martin I., Jiménez-Osés, Gonzalo, Nair, Satish K., and van der Donk, Wilfred A. Mon . "Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease". United States. doi:10.7554/eLife.42305.
@article{osti_1502241,
title = {Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease},
author = {Bobeica, Silvia C. and Dong, Shi-Hui and Huo, Liujie and Mazo, Nuria and McLaughlin, Martin I. and Jiménez-Osés, Gonzalo and Nair, Satish K. and van der Donk, Wilfred A.},
abstractNote = {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.},
doi = {10.7554/eLife.42305},
journal = {eLife},
issn = {2050-084X},
number = 01, 2019,
volume = 8,
place = {United States},
year = {2019},
month = {1}
}