Functional amyloids as inhibitors of plasmid DNA replication

Related Experiment Video

Updated: Mar 21, 2026

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
06:17

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis

Published on: May 22, 2018

12.7K

Laura Molina-García1, Fátima Gasset-Rosa1, María Moreno-Del Álamo1

  • 1Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas - CSIC, E28040 Madrid, Spain.

Scientific Reports
|May 6, 2016
PubMed

Insights

Bacterial plasmid replication is controlled by a handcuffing mechanism involving RepA protein amyloid fibers. This novel amyloid structure directly interacts with DNA, preventing plasmid over-replication and offering a new solution for DNA replication control.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Bacterial plasmids are crucial in clinical, environmental, and biotechnological fields.
  • Plasmid replication control prevents over-replication using mechanisms like handcuffing.
  • RepA protein's WH1 domain can form amyloid fibers, a state linked to diseases but also functional phenotypes in microbes.

Purpose of the Study:

  • To investigate the link between RepA protein handcuffing and amyloid formation.
  • To determine if RepA-mediated handcuffing assemblies exhibit amyloidogenic properties.

Main Methods:

  • Utilized a monoclonal antibody specific to an amyloidogenic conformation of RepA-WH1.
  • Analyzed RepA assemblies reconstructed in vitro.
  • Examined RepA-plasmid complexes within bacterial nucleoids.

Main Results:

  • Handcuffed RepA assemblies, both in vitro and in vivo, were found to be amyloidogenic.
  • This study identifies the first protein amyloid directly interacting with DNA for replication inhibition.
  • RepA-mediated handcuffing represents a functional amyloid structure.

Conclusions:

  • RepA protein's handcuffing mechanism, which inhibits plasmid replication, is amyloidogenic.
  • Amyloid scaffolds can provide novel molecular solutions for controlling DNA replication initiation.
  • This work reveals a new role for protein amyloids in microbial genetic regulation.

More Related Videos

Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease15:23

Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease

Published on: May 13, 2010

20.0K
Rapid Generation of Amyloid from Native Proteins In vitro05:48

Rapid Generation of Amyloid from Native Proteins In vitro

Published on: December 5, 2013

6.6K

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining,...
12.8K
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These...
8
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
17
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
4
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.5K
The Replisome03:01

The Replisome

DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
39.4K