Related Experiment Video
Updated: Apr 23, 2026
Identification of Antibacterial Immunity Proteins in Escherichia coli using MALDI-TOF-TOF-MS/MS and Top-Down Proteomic Analysis
Published on: May 23, 2021
Structure of a bacterial α2-macroglobulin reveals mimicry of eukaryotic innate immunity
11] University Grenoble Alpes, Institut de Biologie Structurale, Grenoble F-38044, France [2] CNRS, IBS, Grenoble F-38044, France [3] CEA, IBS, Grenoble F-38044, France.
Abstract:
Alpha-2-macroglobulins (A2Ms) are plasma proteins that trap and inhibit a broad range of proteases and are major components of the eukaryotic innate immune system. Surprisingly, A2M-like proteins were identified in pathogenically invasive bacteria and species that colonize higher eukaryotes. Bacterial A2Ms are located in the periplasm where they are believed to provide protection to the cell by trapping external proteases through a covalent interaction with an activated thioester. Here we report the crystal structures and characterization of Salmonella enterica ser. Typhimurium A2M in different states of thioester activation. The structures reveal thirteen domains whose arrangement displays high similarity to proteins involved in eukaryotic immune defence. A structural lock mechanism maintains the stability of the buried thioester, a requirement for its protease-trapping activity. These findings indicate that bacteria have developed a rudimentary innate immune system whose mechanism mimics that of eukaryotes.
Insights
Bacteria possess Alpha-2-macroglobulins (A2Ms) that function similarly to eukaryotic immune systems. These bacterial A2Ms trap proteases, revealing a primitive innate immune system in bacteria.
Area of Science:
- Microbiology
- Structural Biology
- Immunology
Background:
- Alpha-2-macroglobulins (A2Ms) are key eukaryotic innate immune proteins that inhibit proteases.
- A2M-like proteins have been found in bacteria, suggesting a conserved function.
- Bacterial A2Ms are located in the periplasm and trap proteases via a covalent thioester interaction.
Purpose of the Study:
- To elucidate the structure and function of bacterial Alpha-2-macroglobulins.
- To investigate the mechanism of protease trapping by bacterial A2Ms.
- To compare bacterial A2M structures with their eukaryotic counterparts.
Main Methods:
- X-ray crystallography of Salmonella enterica ser. Typhimurium A2M in various activation states.
- Biochemical characterization of bacterial A2M activity.
- Structural analysis and comparison with eukaryotic A2Ms.
Main Results:
- Determined crystal structures of Salmonella enterica ser. Typhimurium A2M, revealing thirteen domains.
- Identified a structural lock mechanism that stabilizes the thioester for protease trapping.
- Demonstrated high structural similarity between bacterial and eukaryotic immune defense proteins.
Conclusions:
- Bacterial A2Ms possess a structure analogous to eukaryotic immune proteins.
- Bacteria have evolved a rudimentary innate immune system that mimics eukaryotic mechanisms.
- The findings suggest convergent evolution of immune defense strategies across different domains of life.
Related Concept Videos
01:31Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:10Antibody Structure
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
01:10Antibody Structure
01:26Antigens Involved in Adaptive Immunity
Complete Antigens
Complete antigens possess both immunogenicity and...
01:25Antibody Structure and Classes
The basic structure of an antibody consists of four protein chains: two identical heavy chains and two identical light chains. These chains are held together by disulfide bonds and other non-covalent interactions, forming a Y-shaped structure.
01:24B Cell Activation and Differentiation
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...