title: Synergistic binding of the leader and core peptides by the lantibiotic synthetase HalM2.
abstract: Lanthipeptides are a class of ribosomally produced and post-translationally modified peptides (RiPPs) that possess a variety of biological activities but typically act as antimicrobial agents (lantibiotics). Haloduracin is a lantibiotic that is composed of two post-translationally modified peptides, Halα and Halβ, which are biosynthesized from the precursor peptides HalA1 and HalA2 by their cognate lanthipeptide synthetases, HalM1 and HalM2, respectively. Coexpression studies of HalM1 and HalM2 with chimeric peptides consisting of the leader peptide of HalA1 and the core peptide of HalA2 (or vice versa) showed that the synthetases require both the cognate leader and core peptides for efficient processing. Investigation of the affinity in vitro showed that binding of the N-terminal leader peptide by HalM2 increases its affinity for the C-terminal core peptide. Thus, the two segments of the precursor peptide HalA2 synergistically bind to HalM2.
authors.affiliation: †Howard Hughes Medical Institute and Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Gabrielle N
authors.initials: GN
authors.lastname: Thibodeaux
authors.affiliation: †Howard Hughes Medical Institute and Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: McClerren
authors.affiliation: †Howard Hughes Medical Institute and Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Ma
authors.affiliation: ‡Summer Research Opportunities Program at UIUC, Department of Chemistry, San Jose State University, San Jose, California 95129, United States.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Gancayco
authors.affiliation: †Howard Hughes Medical Institute and Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United States.
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: van der Donk
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001430:Bacteriocins / Q000378:metabolism*; D001665:Binding Sites; D005454:Fluorescence Polarization; D008025:Ligases / Q000737:chemistry* / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D001430:Bacteriocins; D021382:Protein Sorting Signals; C515824:haloduracin, Bacillus halodurans; D008025:Ligases