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Updated: May 24, 2026
08:57
Aip1p Dynamics Are Altered by the R256H Mutation in Actin
Published on: July 30, 2014
A structural basis for regulation of actin polymerization by pectenotoxins
John S Allingham1, Christopher O Miles, Ivan Rayment
1Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Journal of Molecular Biology
|June 30, 2007
Summary
Palytoxins (PTXs) disrupt the actin cytoskeleton by binding to a unique site on actin monomers. This interaction caps filament growth, offering a novel mechanism for PTX toxicity and potential for analogue development.
Area of Science:
- Biochemistry
- Toxicology
- Structural Biology
Background:
- Palytoxins (PTXs) are marine toxins linked to diarrhetic shellfish poisoning and cancer cell cytotoxicity.
- Previous research suggested PTXs disrupt the actin cytoskeleton, but the molecular mechanism remained unclear.
Purpose of the Study:
- To elucidate the molecular mechanism of PTX-2's interaction with actin.
- To provide a structural basis for PTX toxicity and structure-activity relationships.
Main Methods:
- X-ray crystallography of PTX-2 bound to actin.
- Analysis of PTX-2's effect on purified actin filament dynamics.
Main Results:
- PTX-2 forms a 1:1 complex with actin at a novel binding site between subdomains 1 and 3.
- PTX-2 binding disrupts lateral monomer contacts, capping the barbed-end of actin filaments without severing them.
- This capping mechanism is unique compared to other actin-destabilizing toxins.
Conclusions:
- The crystal structure reveals PTX-2's unique molecular mechanism of actin disruption.
- This finding explains PTX toxicity and provides a basis for predicting the toxicity of PTX analogues.
Related Concept Videos
01:26Introduction to Actin
Actin is a highly conserved cytoskeletal protein found abundantly in eukaryotic cells. It constitutes 10% weight of the total cellular protein in muscle cells, while in non-muscle cells, it is lower and makes up around 1–5 percent of the total cell protein. Actin found in the unicellular amoebae and complex multicellular animals is around 80% similar, demonstrating their conservation over a billion years of evolution. Actin coding genes are conserved within species and across different species.
01:42Actin Polymerization
Actin polymerization occurs through the head-to-tail association of binding sites on monomeric actin or G-actin to form filamentous or F-actin. The polymerization can be divided into three phases ̶ nucleation, elongation, and steady-state phase.
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight actin...
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight actin...
01:14Generation of Straight or Branched Actin Filaments
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
01:19Actin Filament Depolymerization
Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
In F-actin, the ADF/cofilin proteins...
01:11Formation of Higher-order Actin Filaments
The polymerization of G-actin monomers into filamentous F-actin is a multi-step process. Once the F-actins are formed, they can bundle together in different arrangements to form higher-order networks and regulate cellular functions. Common examples include the formation of lamellipodia and filopodia at the cell's leading edge by actin reorganization in a migrating cell. The microvilli on the brush border epithelial cells are also formed through the F-actin network.
The high-order actin networks...
The high-order actin networks...
01:13Actin Polymerization and Cell Motility
Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate.