Insights into AMS/PCAT transporters from biochemical and structural characterization of a double Glycine motif protease.
Bobeica, S.C., Dong, S., Huo, L., Mazo, N., McLaughlin, M.I.H., Jimenez-Oses, G., Nair, S.K., van der Donk, W.A.(2019) Elife 8
- PubMed: 30638446 
- DOI: https://doi.org/10.7554/eLife.42305
- Primary Citation of Related Structures:  
6MPZ - PubMed 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.
Organizational Affiliation: 
Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, United States.