Related Experiment Video

Updated: May 22, 2025

Aip1p Dynamics Are Altered by the R256H Mutation in Actin
08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

7.9K

Dynamical features of smooth muscle actin pathological mutants: The arginine-257(258)-Cysteine cases

F Chiappori1, F Di Palma2, A Cavalli2,3

  • 1National Research Council, Institute for Biomedical Technologies, Segrate, MI, Italy.

Computational and Structural Biotechnology Journal
|March 17, 2025
PubMed

Insights

The R257(8)C mutation destabilizes actin filaments, impacting visceral and vascular muscle function. This study uses molecular dynamics to reveal how this mutation causes severe genetic diseases like myopathy and aortic dissections.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • The R257(8)C mutation in ACTG2 and ACTA2 is a primary cause of severe genetic disorders.
  • These disorders include visceral myopathy and familial thoracic aortic aneurysms and dissections, affecting visceral and vascular smooth muscle.
  • The precise molecular mechanisms driving these pathologies remain unclear.

Purpose of the Study:

  • To investigate the structural and dynamic effects of the R257(8)C mutation in actin.
  • To elucidate the molecular mechanisms underlying actin-related genetic diseases using computational methods.

Main Methods:

  • Utilized molecular dynamics simulations to analyze wild-type (WT) and mutated actin monomers (g-actin) and filaments (f-actin).
  • Compared the structural integrity and dynamics of WT and R257(8)C mutated actin.

Main Results:

  • Monomeric (g-) actins showed no significant folding differences between WT and mutated forms.
  • Mutated actin filaments (f-actin) exhibited destabilization.
  • R257C f-ACTG2 subunits adopted suboptimal angles, and R258C f-ACTA2 showed depolymerization during simulations.

Conclusions:

  • The R257(8)C mutation critically affects actin structure and dynamics, particularly within actin filaments.
  • These findings highlight the importance of residue R257(8) in maintaining actin filament stability and function.
  • The study provides insights into the molecular basis of actin-related myopathies and aortic diseases.
Keywords:
ACTA2ACTG2Aortic aneurysmMolecular dynamicsVisceral Myopathy

More Related Videos

Author Spotlight: Functional Site-Directed Fluorometry in Native Cells to Study Skeletal Muscle Excitability12:26

Author Spotlight: Functional Site-Directed Fluorometry in Native Cells to Study Skeletal Muscle Excitability

Published on: June 2, 2023

892
Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro08:28

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro

Published on: February 15, 2022

3.5K

Related Concept Videos

Actin Polymerization and Cell Motility01:13

Actin 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....
5.0K
Smooth Muscle Contraction01:25

Smooth Muscle Contraction

Smooth muscle contraction is a complex process vital for various bodily functions, from maintaining blood vessel tension to facilitating the movement of food through the digestive tract. Unlike striated muscles, smooth muscle contraction begins more slowly and lasts longer.
The onset of contraction is triggered by an increase in calcium ions within the sarcoplasm, similar to the process in striated muscle. However, smooth muscles have a relatively smaller reservoir of the sarcoplasmic...
2.3K
Introduction to Actin01:26

Introduction 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...
4.8K
Actin Filament Depolymerization01:19

Actin 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...
3.0K
Cross-bridge Cycle01:26

Cross-bridge Cycle

As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
116.5K
The Sarcomere01:08

The Sarcomere

A sarcomere is a microscopic segment repeating in a myofibril. The sarcomere fundamentally consists of two main myofilaments: thick filaments called myosin and thin filaments called actin. These filaments interact by sliding past each other in response to stimulus. In addition to myosin and actin, several other proteins, such as tropomyosin, troponin, titin, nebulin, myomesin, α-actinin, and dystrophin, play crucial roles in regulating, structuring, and functioning of the sarcomere.
Each...
7.4K