Related Experiment Video

Updated: Mar 26, 2026

Production and Visualization of Bacterial Spheroplasts and Protoplasts to Characterize Antimicrobial Peptide Localization
10:13

Production and Visualization of Bacterial Spheroplasts and Protoplasts to Characterize Antimicrobial Peptide Localization

Published on: August 11, 2018

12.9K

Structure of the mammalian antimicrobial peptide Bac7(1-16) bound within the exit tunnel of a bacterial ribosome

A Carolin Seefeldt1, Michael Graf2, Natacha Pérébaskine1

  • 1Institut Européen de Chimie et Biologie, University of Bordeaux, Pessac 33607, France U1212, Inserm, Bordeaux 33076, France UMR 5320, CNRS, Bordeaux 33076, France.

Nucleic Acids Research
|January 22, 2016
PubMed

Insights

Proline-rich antimicrobial peptides (PrAMPs) show potential against drug-resistant bacteria by inhibiting translation. However, this study reveals mammalian Bac7 inhibits both bacterial and mammalian ribosomes, necessitating careful drug development.

Area of Science:

  • Structural biology
  • Biochemistry
  • Microbiology

Background:

  • Proline-rich antimicrobial peptides (PrAMPs) are part of innate immunity and a potential resource against multidrug-resistant bacteria.
  • PrAMPs like oncocin and bactenecin-7 (Bac7) inhibit bacterial translation, but their specificity is unclear, impacting drug development safety.
  • Understanding PrAMP-ribosome interactions is crucial for developing safe and effective antimicrobial drugs.

Purpose of the Study:

  • To elucidate the structural basis of PrAMP interaction with bacterial ribosomes.
  • To investigate the specificity of mammalian Bac7 and insect-derived PrAMPs (metalnikowin I, pyrrhocoricin) on bacterial and mammalian ribosomes.
  • To understand the mechanism of translation inhibition by Bac7.

Main Methods:

  • X-ray crystallography to determine the structures of Thermus thermophilus 70S ribosome complexed with mammalian Bac7 and insect PrAMPs.
  • Biochemical assays to assess the competition of PrAMPs with antibiotics targeting the ribosomal exit tunnel.
  • In vitro translation assays to evaluate the effect of Bac7 on translation initiation and elongation.

Main Results:

  • Crystal structures reveal mammalian Bac7 binds to a similar ribosomal site as insect PrAMPs.
  • Bac7 and oncocin derivative Onc112 compete with exit tunnel-targeting antibiotics like erythromycin.
  • Bac7 inhibits translation by blocking the elongation phase and affects both bacterial and mammalian ribosomes.

Conclusions:

  • Mammalian Bac7 inhibits translation on both bacterial and mammalian ribosomes, explaining its pro-peptide storage.
  • PrAMP specificity for bacterial ribosomes needs careful consideration in drug development.
  • Structural insights into PrAMP-ribosome interactions guide future antimicrobial drug design.

More Related Videos

Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses11:19

Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses

Published on: February 25, 2011

20.4K
From Constructs to Crystals – Towards Structure Determination of β-barrel Outer Membrane Proteins09:55

From Constructs to Crystals – Towards Structure Determination of β-barrel Outer Membrane Proteins

Published on: July 4, 2016

14.2K

Related Concept Videos

Termination of Translation01:44

Termination of Translation

The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
28.5K
Multi-pass Transmembrane Proteins and β-barrels01:09

Multi-pass Transmembrane Proteins and β-barrels

In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
6.8K
Insertion of Single-pass Transmembrane Proteins in the RER01:26

Insertion of Single-pass Transmembrane Proteins in the RER

Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
18.8K
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
33
Cotranslational Protein Translocation01:20

Cotranslational Protein Translocation

Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
10.9K
Bacterial Translocation and Protein Secretion01:26

Bacterial Translocation and Protein Secretion

Bacterial protein secretion involves translocation systems to ensure proteins reach their designated locations, including the plasma membrane, periplasm, outer membrane, or the external environment. These translocation systems are vital for bacterial physiology, supporting processes like membrane assembly, enzymatic activity in the periplasm, and interactions with the external environment. The division of labor between Sec and Tat pathways ensures efficiency in handling proteins with diverse...
981