Related Experiment Video
Updated: Jun 12, 2026
12:26
Functional Site-Directed Fluorometry in Native Cells to Study Skeletal Muscle Excitability
Published on: June 2, 2023
A helix replacement mechanism directs metavinculin functions
Erumbi S Rangarajan1, Jun Hyuck Lee, S D Yogesha
1Cell Adhesion Laboratory, Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, United States of America.
Plos One
|May 27, 2010
Summary
Metavinculin, a vinculin isoform, has unique functions due to a structural helix replacement in its tail domain. This mechanism is crucial for muscle health and mutations cause fatal cardiomyopathies.
Area of Science:
- Cell biology
- Structural biology
- Biochemistry
Background:
- Vinculin is essential for linking cell adhesion complexes to the actin cytoskeleton.
- Metavinculin, a vinculin isoform, possesses unique properties and plays critical roles in muscle development and homeostasis.
- Mutations in metavinculin's unique insert are linked to fatal cardiomyopathies.
Purpose of the Study:
- To elucidate the structural basis of metavinculin's distinct functions.
- To investigate the structural mechanisms underlying metavinculin-associated cardiomyopathies.
Main Methods:
- High-resolution crystal structure determination of metavinculin domains and full-length protein.
- Structural analysis of a cardiomyopathy-associated deletion mutant (DeltaLeu954).
- Biochemical assays to assess actin bundling and oligomerization properties.
Main Results:
- The metavinculin tail domain features a novel five-helix bundle structure.
- A unique alpha-helix (H1') and extended coil from the metavinculin insert replace elements found in vinculin's tail.
- This helix replacement mechanism dictates metavinculin's distinct actin-binding and oligomerization capabilities.
- Cardiomyopathy-associated mutations (DeltaLeu954, Arg975Trp) are located within this altered structural region.
Conclusions:
- A helix replacement mechanism in the metavinculin tail domain underlies its unique functional properties.
- Structural alterations in metavinculin are directly implicated in the pathogenesis of cardiomyopathies.
- Understanding these structural-biochemical relationships provides insights into muscle disease mechanisms.
Related Concept Videos
01:32Pinching-off of Coated Vesicles
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
01:19Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
00:55DNA Helicases
DNA unwinding helicase enzymes are a type of motor protein. Motor proteins can translocate along filaments or polymers using energy generated from ATP hydrolysis. Helicases are involved in all the important cellular processes where DNA unwinding is required, such as DNA replication, repair, recombination, and transcription. They are present in all living organisms, but vary in their structure, function, and mechanism of action. For example, in prokaryotes, DnaB helicase binds and translocates...
01:39Mechanism of Filopodia Formation
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
01:26Tension Response at Adherens Junctions
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...
01:34Directing Proteins to the Rough Endoplasmic Reticulum
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...