9WJU

Cryo-EM structure of the L. garvieae Man-PTS in complex with the bacteriocin GarQ

Summary for 9WJU

• Entry DOI: 10.2210/pdb9wju/pdb
• EMDB information: 66027 66030
• Descriptor: Mannose/fructose/sorbose family PTS transporter subunit IIC, PTS mannose transporter subunit IID, Prepeptide GarQ, ... (4 entities in total)
• Functional Keywords: antibiotic resistance; antimicrobial peptides; mannose phosphotransferase system; man-pts; bacteriocins; non-pediocin-like/class iid bacteriocins; garvicin q; garq, membrane protein
• Biological source: Lactococcus garvieae; More
• Total number of polymer chains: 7
• Total formula weight: 205920.61

Authors

Wang, J.W. (deposition date: 2025-08-31, release date: 2025-11-12, Last modification date: 2026-03-11)

Primary citation

Duan, J.,Li, D.,Zhao, Y.,Wang, J.
Structural basis for the extended-spectrum antimicrobial activity of Garvieacin Q.
Appl.Environ.Microbiol., 92:e0177325-e0177325, 2026

PubMed Abstract: Class IIa and IId bacteriocins are antimicrobial peptides with potential for combating antibiotic-resistant pathogens. However, their species-specific activity, dictated by recognition of the mannose phosphotransferase system (Man-PTS) receptor, often restricts their spectrum. Garvieacin Q/Garvicin Q (GarQ), a newly identified class IId bacteriocin, is unusual in that it targets both and the non-lactococcal pathogen , yet the structural basis for this cross-species activity has remained unclear. Using cryo-electron microscopy, we determined the structures of GarQ bound to Man-PTS receptors from and . In , the receptor contains a unique Tudor-like γ+ domain that sterically constrains the N terminus of incoming bacteriocins, thereby enforcing specificity for GarQ while excluding others such as lactococcin A (LcnA). In , GarQ engages the receptor through the same conserved binding mode, effectively bypassing the unusual species barrier. We further demonstrate that the C-terminal length of GarQ is a critical determinant of pore size and target specificity. Together, these findings uncover the structural mechanism underlying GarQ's atypical extended-spectrum activity and provide a framework for engineering bacteriocins with customized spectra to combat specific pathogens.IMPORTANCEThis study establishes a structural basis for how the extended-spectrum bacteriocin Garvieacin Q (GarQ) circumvents the canonical species-specificity of class II bacteriocins by engaging mannose phosphotransferase system receptors from different bacterial genera through both conserved and divergent binding modes. We identify a previously unknown Tudor-like γ+ domain in the receptor that sterically restricts the access of other bacteriocins, thereby defining bacteriocin specificity. Moreover, we demonstrate that the C-terminal length of GarQ critically determines pore size and bacterial targets, revealing an engineerable principle for designing synthetic bacteriocins with customized spectra against clinically relevant pathogens.

PubMed: 41562606
DOI: 10.1128/aem.01773-25

Experimental method

ELECTRON MICROSCOPY (3.81 Å)