Related Experiment Video

Updated: Mar 25, 2026

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
06:45

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

Published on: May 26, 2011

15.7K

Localization of the binding interface between leiomodin-2 and α-tropomyosin

Mert Colpan1, Dmitri Tolkatchev1, Samantha Grover1

  • 1Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA 99164-6515, USA.

Biochimica Et Biophysica Acta
|February 14, 2016
PubMed

Insights

Familial dilated cardiomyopathy (DCM) links to mutations affecting cardiac muscle thin filaments. A K15N mutation in α-tropomyosin disrupts interactions with leiomodin-2, explaining DCM development.

Area of Science:

  • Cardiovascular Biology
  • Molecular Muscle Physiology
  • Protein Interaction Studies

Background:

  • Familial dilated cardiomyopathy (DCM) is linked to mutations in cardiac muscle thin filament proteins.
  • Uncharacterized protein-protein interactions may underlie the harmful effects of these mutations.

Purpose of the Study:

  • To identify the interaction region between striated muscle α-tropomyosin (Tpm1.1) and leiomodin-2 (Lmod2).
  • To investigate the impact of the familial DCM-associated K15N mutation in Tpm1.1 on Lmod2 and Tmod1 binding.

Main Methods:

  • Nuclear magnetic resonance (NMR) spectroscopy was used to map the Tpm1.1-Lmod2 interaction site.
  • Binding affinities of wild-type and K15N mutant Tpm1.1 to Lmod2 and Tmod1 were assessed.

Main Results:

  • The N-terminal 21 residues of Tpm1.1 interact with residues 7-41 of Lmod2.
  • The K15N mutation in Tpm1.1, located in the Lmod2 binding site, significantly reduced binding affinity for both Lmod2 and Tmod1.
  • Lmod2 and Tmod1 are crucial for regulating thin filament length in cardiac muscle.

Conclusions:

  • The K15N mutation impairs Tpm1.1 interactions with Lmod2 and Tmod1.
  • This disruption provides a molecular explanation for the pathogenesis of familial DCM.
Keywords:
Circular dichroismDilated cardiomyopathyIntrinsically disordered regionsLeiomodinNuclear magnetic resonanceTropomodulin

More Related Videos

Detection of In Situ Protein-protein Complexes at the Drosophila Larval Neuromuscular Junction Using Proximity Ligation Assay10:31

Detection of In Situ Protein-protein Complexes at the Drosophila Larval Neuromuscular Junction Using Proximity Ligation Assay

Published on: January 20, 2015

13.9K
Analysis of Cardiomyocyte Development using Immunofluorescence in Embryonic Mouse Heart10:56

Analysis of Cardiomyocyte Development using Immunofluorescence in Embryonic Mouse Heart

Published on: March 26, 2015

22.2K

Related Concept Videos

Conserved Binding Sites01:49

Conserved Binding Sites

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...
5.3K
Overview of Myosin Structure and Function01:15

Overview of Myosin Structure and Function

Myosins are a family of molecular motor proteins, first identified in the skeletal muscles, where they are responsible for muscle contraction. Along with their role in muscle contraction, these proteins also play a role in the intracellular transport of molecules and vesicles. There are twenty-four classes of myosins based on their domain sequence and organization. Of the twenty-four, six classes (Myosin I, Myosin II, Myosin V, Myosin VI, Myosin VII, and Myosin X)  have been well...
7.3K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.9K
Protein-protein Interfaces02:04

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
15.0K
Protein-Protein Interfaces02:04

Protein-Protein Interfaces

4.6K
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...
19.6K