Structure and dynamics of cardiotoxins
Anastasia G Konshina1, Peter V Dubovskii, Roman G Efremov
1Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya str., 117997 GSP, Moscow V-437, Russia.
Insights
Cytotoxins (CTs) from cobra venom, known for their three-finger fold, are amphiphilic peptides. This review explores their structure and dynamics, suggesting membrane interactions drive their cytotoxic effects.
Area of Science:
- Biochemistry
- Toxicology
- Structural Biology
Background:
- Cytotoxins (CTs) are 60-residue peptides from cobra venom, featuring a characteristic three-finger (TF) fold and disulfide bonds.
- Unlike neurotoxins (NTs), CTs lack specific protein targets but exhibit amphiphilic properties and cytotoxicity against various cells, including cancer cells.
Purpose of the Study:
- To review experimental and computational data on the spatial organization and dynamics of cytotoxins.
- To elucidate the molecular basis of CT toxicity, particularly their interactions with lipid membranes.
Main Methods:
- Summary of existing experimental data on CT structure and dynamics.
- Compilation of computational studies investigating CT behavior in different environments.
Main Results:
- CTs possess a conserved three-finger fold stabilized by disulfide bonds, with β-structures forming loops.
- CTs are amphiphilic, suggesting their primary mechanism of action involves interactions with lipid membranes rather than specific protein receptors.
- Variations in CT toxicity are linked to their structural and dynamic properties in different environments.
Conclusions:
- The central hypothesis posits that CT activity stems from interactions with lipid membranes.
- Understanding CT structure and dynamics is crucial for deciphering variations in their toxicity.
- Further research into CT-membrane interactions is warranted to understand their cytotoxic effects.
Abstract:
Cytotoxins (or cardiotoxins; CTs) are toxins from cobra venom characterized by the three-finger (TF) fold. CTs are on average 60-residue-long peptides, possessing as many as 4 disulfide bonds. The elements of antiparallel β-structure take origin from the hydrophobic core formed by the disulfides. The β-strands adopt the shape of the three loops, giving the name of the fold. While neurotoxins (NTs) - also TF proteins from snake venom - exert their effect through specific interactions with protein receptors, no specific protein target has been found for CTs. Unlike NTs, CTs are amphiphilic and cytotoxic against a variety of cells, including cancer ones. Thus, the hypothesis that the activity of CTs is caused by their interactions with lipid membranes is currently central. To understand molecular basis behind variations in toxicities of CTs highly homologous in their sequences, detailed knowledge of their structure and dynamics is required. The present review summarizes experimental and computational data on the spatial organization of CTs and their dynamics in various environments (aqueous solution, membranous milieus).
Related Concept Videos
01:12Bacterial Toxins
01:36Types of Toxins
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
01:19Electrophysiology of Normal Cardiac Rhythm
01:13Structure of Cardiac Muscles
Compared to skeletal muscles, cardiac muscle cells are small and mostly have a single nucleus. Additionally, they are usually...
01:27Specialized Characteristics of Cardiac Muscles
Cardiac muscle cells are smaller than skeletal muscles, averaging 10–20 mm in diameter and 50–100 mm in length. However, they have large energy demands for continuous contraction and relaxation. This energy is almost exclusively derived from aerobic metabolism of energy reserves in...
01:28Mechanism of Cardiac Arrhythmias