Related Experiment Video
Updated: Sep 20, 2025
05:29
Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry
Published on: March 24, 2023
4.7K
Comparing the folding landscapes of evolutionarily divergent procaspase-3
1Department of Biology, University of Texas at Arlington, Arlington, Texas 76019, U.S.A.
Bioscience Reports
|June 7, 2022
Summary
The folding landscape of apoptotic caspases is conserved across species, though differences exist in folding intermediates. This conservation suggests a common evolutionary path for caspase function.
Area of Science:
- Biochemistry
- Evolutionary Biology
- Molecular Biology
Background:
- Caspases, crucial for apoptosis and inflammation, evolved from a common ancestor.
- The caspase-hemoglobinase fold is conserved in both monomeric (initiator) and dimeric (effector) apoptotic caspases.
Purpose of the Study:
- To investigate the evolutionary conservation of the folding landscape in effector caspases.
- To compare the folding and assembly of zebrafish procaspase-3b with human effector procaspases.
Main Methods:
- Urea-induced equilibrium folding/unfolding experiments were performed on zebrafish procaspase-3b.
- Comparative analysis of effector caspases across different species was conducted.
Main Results:
- Zebrafish procaspase-3b exhibits a three-state folding pathway, differing from human procaspase-3 by the underpopulation of a monomeric intermediate.
- Effector procaspase dimers undergo a conserved pH-dependent conformational change, impacting their stability and activity.
Conclusions:
- The caspase-hemoglobinase fold landscape is conserved, allowing for species-specific adaptations in stability.
- A pH-dependent conformational change offers a reversible mechanism for regulating caspase activity.
Related Concept Videos
01:24Caspases
12.7K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.7K
01:25Protein Folding
8.8K
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
8.8K
03:00Molecular Chaperones and Protein Folding
18.5K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
18.5K
01:31The Intrinsic Apoptotic Pathway
6.9K
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...
6.9K
01:49Conserved Binding Sites
4.4K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.4K
02:54Evolutionary Relationships through Genome Comparisons
6.2K
Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
6.2K