Related Experiment Video

Updated: Jun 21, 2026

Analyzing Dynamic Protein Complexes Assembled On and Released From Biolayer Interferometry Biosensor Using Mass Spectrometry and Electron Microscopy
09:30

Analyzing Dynamic Protein Complexes Assembled On and Released From Biolayer Interferometry Biosensor Using Mass Spectrometry and Electron Microscopy

Published on: August 6, 2018

The anthrax lethal factor and its MAPK kinase-specific metalloprotease activity

Fiorella Tonello1, Cesare Montecucco

  • 1Dipartimento di Scienze Biomediche Sperimentali, Istituto CNR di Neuroscienze, Università di Padova, Viale G. Colombo 3, 35131 Padova, Italy.

Molecular Aspects of Medicine
|August 12, 2009
PubMed

Insights

Anthrax lethal factor (LF) disrupts cell signaling by cleaving MAPK kinases. Researchers review LF

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Toxicology

Background:

  • Bacillus anthracis releases the anthrax lethal factor (LF), a multi-domain protein toxin.
  • LF enters host cells via protective antigen and cell receptors.
  • LF targets MAPK kinases in the cytosol, disrupting cell signaling pathways.

Purpose of the Study:

  • To review the structural features of LF responsible for its activity.
  • To focus on LF's proteolytic activity and potential inhibitors.
  • To discuss structural similarities between LF and clostridial neurotoxins.

Main Methods:

  • Literature review of structural and functional studies on anthrax lethal factor.
  • Comparative analysis of metalloprotease domains.

Main Results:

  • LF cleaves the N-terminal tail of numerous MAPK kinases.
  • Structural similarities exist between LF's metalloprotease domain and those of clostridial neurotoxins.
  • Potential inhibitors for LF's proteolytic activity have been identified.

Conclusions:

  • LF's structural characteristics underpin its cell-disrupting proteolytic activity.
  • Understanding LF structure aids in developing targeted inhibitors.
  • The metalloprotease domain homology suggests shared mechanisms with other toxins.

More Related Videos

Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major08:17

Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major

Published on: October 28, 2022

Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses08:38

Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses

Published on: February 22, 2019

Related Concept Videos

Inhalation Anthrax01:25

Inhalation Anthrax

Anthrax is a zoonotic disease caused by Bacillus anthracis, a Gram-positive, spore-forming bacterium. It primarily affects herbivorous animals but can be transmitted to humans through skin contact, ingestion, or inhalation of spores.Cutaneous anthrax, the most common form, typically results from direct contact with bacterial spores through skin abrasions and is generally less severe. Gastrointestinal anthrax results from eating undercooked or contaminated meat. It affects the mouth, throat, or...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Bacterial Toxins01:12

Bacterial Toxins

Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Determinants of Bacterial Pathogenicity and Virulence01:20

Determinants of Bacterial Pathogenicity and Virulence

Pathogenic bacteria employ a variety of strategies to establish infections, including the secretion of extracellular enzymes that act as potent virulence factors. These enzymes facilitate bacterial colonization of host tissues and help evade immune surveillance. By targeting structural components of host tissues and interfering with immune mechanisms, these enzymes play a pivotal role in disease progression.Extracellular Enzymes Facilitating Tissue Invasion: Several bacterial pathogens secrete...