Structural Basis for Natural Product Selection and Export by Bacterial ABC Transporters

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Bacteria synthesize ribosomally synthesized and post-translationally modified peptides (RiPPs) for inter-species competition.
• These RiPPs, like microcin J25 (MccJ25), can be toxic to producing bacteria, necessitating self-immunity mechanisms.
• Dedicated ABC transporters, such as McjD in Escherichia coli, are responsible for exporting toxic RiPPs and conferring self-immunity.

Purpose of the Study:

• To elucidate the recognition mechanism between the toxic lasso peptide MccJ25 and its cognate ABC transporter, McjD.
• To investigate the specificity of McjD for MccJ25 compared to other RiPPs and antibiotics.
• To understand the structural basis for specificity in natural product ABC transporters.

Main Methods:

• Biomolecular Nuclear Magnetic Resonance (NMR) spectroscopy was employed to study the interaction between MccJ25 and McjD.
• Structural and functional analyses were performed to identify key regions involved in peptide recognition.
• Comparative studies were conducted using other RiPPs and antibiotics to assess transporter specificity.

Main Results:

• A specific region of MccJ25 was identified as critical for recognition by the McjD ABC transporter.
• McjD demonstrated high specificity for MccJ25, distinguishing it from other RiPPs and antibiotics.
• MccJ25 was not exported by a different natural product ABC transporter, further highlighting McjD's specificity.

Conclusions:

• Specific interactions between natural product ABC transporters and their substrates are key to achieving high specificity.
• The binding cavity of ABC transporters may possess structural elements that enable recognition of specific natural products.
• These findings contribute to understanding bacterial defense mechanisms and the evolution of ABC transporters.