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

Silvia C. Bobeica, Shi Hui Dong, Liujie Huo, Nuria Mazo, Martin I. McLaughlin, Gonzalo Jiménez-Osés, Satish K Nair, Wilfred Adrianus van der Donk

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Jan 14 2019

Fingerprint

Protein Sorting Signals
Glycine
Peptide Hydrolases
Bacteria
Peptides
Substrates
ATP-Binding Cassette Transporters
Gram-Positive Bacteria
Operon
Gram-Negative Bacteria
Crystal structure
Proteins
C 39

Keywords

  • AMC transporter
  • Lachnospiraceae
  • biochemistry
  • chemical biology
  • leader peptide
  • protease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease. / Bobeica, Silvia C.; Dong, Shi Hui; Huo, Liujie; Mazo, Nuria; McLaughlin, Martin I.; Jiménez-Osés, Gonzalo; Nair, Satish K; van der Donk, Wilfred Adrianus.

In: eLife, Vol. 8, 14.01.2019.

Research output: Contribution to journalArticle

Bobeica, Silvia C. ; Dong, Shi Hui ; Huo, Liujie ; Mazo, Nuria ; McLaughlin, Martin I. ; Jiménez-Osés, Gonzalo ; Nair, Satish K ; van der Donk, Wilfred Adrianus. / Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease. In: eLife. 2019 ; Vol. 8.
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