The structure of isolated cardiac myosin thick filaments from cardiac myosin binding protein-C knockout mice

Robert W. Kensler, Samantha - Harris

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Mutations in the thick filament associated protein cardiac myosin binding protein-C (cMyBP-C) are a major cause of familial hypertrophic cardiomyopathy. Although cMyBP-C is thought to play both a structural and a regulatory role in the contraction of cardiac muscle, detailed information about the role of this protein in stability of the thick filament and maintenance of the ordered helical arrangement of the myosin cross-bridges is limited. To address these questions, the structure of myosin thick filaments isolated from the hearts of wild-type mice containing cMyBP-C (cMyBP-C +/+) were compared to those of cMyBP-C knockout mice lacking this protein (cMyBp-C -/-). The filaments from the knockout mice hearts lacking cMyBP-C are stable and similar in length and appearance to filaments from the wild-type mice hearts containing cMyBP-C. Both wild-type and many of the cMyBP-C -/- filaments display a distinct 43 nm periodicity. Fourier transforms of electron microscope images typically show helical layer lines to the sixth layer line, confirming the well-ordered arrangement of the cross-bridges in both sets of filaments. However, the "forbidden" meridional reflections, thought to derive from a perturbation from helical symmetry in the wild-type filament, are weaker or absent in the transforms of the cMyBP-C -+- myocardial thick filaments. In addition, the cross-bridge array in the absence of cMyBP-C appears more easily disordered.

Original languageEnglish (US)
Pages (from-to)1707-1718
Number of pages12
JournalBiophysical Journal
Volume94
Issue number5
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Fingerprint

Cardiac Myosins
Knockout Mice
Myosins
Familial Hypertrophic Cardiomyopathy
myosin-binding protein C
Protein Stability
Periodicity
Fourier Analysis
Protein C
Myocardium
Maintenance
Electrons

ASJC Scopus subject areas

  • Biophysics

Cite this

The structure of isolated cardiac myosin thick filaments from cardiac myosin binding protein-C knockout mice. / Kensler, Robert W.; Harris, Samantha -.

In: Biophysical Journal, Vol. 94, No. 5, 01.03.2008, p. 1707-1718.

Research output: Contribution to journalArticle

@article{237c809ff1ea4ffba7060e1eba846abe,
title = "The structure of isolated cardiac myosin thick filaments from cardiac myosin binding protein-C knockout mice",
abstract = "Mutations in the thick filament associated protein cardiac myosin binding protein-C (cMyBP-C) are a major cause of familial hypertrophic cardiomyopathy. Although cMyBP-C is thought to play both a structural and a regulatory role in the contraction of cardiac muscle, detailed information about the role of this protein in stability of the thick filament and maintenance of the ordered helical arrangement of the myosin cross-bridges is limited. To address these questions, the structure of myosin thick filaments isolated from the hearts of wild-type mice containing cMyBP-C (cMyBP-C +/+) were compared to those of cMyBP-C knockout mice lacking this protein (cMyBp-C -/-). The filaments from the knockout mice hearts lacking cMyBP-C are stable and similar in length and appearance to filaments from the wild-type mice hearts containing cMyBP-C. Both wild-type and many of the cMyBP-C -/- filaments display a distinct 43 nm periodicity. Fourier transforms of electron microscope images typically show helical layer lines to the sixth layer line, confirming the well-ordered arrangement of the cross-bridges in both sets of filaments. However, the {"}forbidden{"} meridional reflections, thought to derive from a perturbation from helical symmetry in the wild-type filament, are weaker or absent in the transforms of the cMyBP-C -+- myocardial thick filaments. In addition, the cross-bridge array in the absence of cMyBP-C appears more easily disordered.",
author = "Kensler, {Robert W.} and Harris, {Samantha -}",
year = "2008",
month = "3",
day = "1",
doi = "10.1529/biophysj.107.115899",
language = "English (US)",
volume = "94",
pages = "1707--1718",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "5",

}

TY - JOUR

T1 - The structure of isolated cardiac myosin thick filaments from cardiac myosin binding protein-C knockout mice

AU - Kensler, Robert W.

AU - Harris, Samantha -

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Mutations in the thick filament associated protein cardiac myosin binding protein-C (cMyBP-C) are a major cause of familial hypertrophic cardiomyopathy. Although cMyBP-C is thought to play both a structural and a regulatory role in the contraction of cardiac muscle, detailed information about the role of this protein in stability of the thick filament and maintenance of the ordered helical arrangement of the myosin cross-bridges is limited. To address these questions, the structure of myosin thick filaments isolated from the hearts of wild-type mice containing cMyBP-C (cMyBP-C +/+) were compared to those of cMyBP-C knockout mice lacking this protein (cMyBp-C -/-). The filaments from the knockout mice hearts lacking cMyBP-C are stable and similar in length and appearance to filaments from the wild-type mice hearts containing cMyBP-C. Both wild-type and many of the cMyBP-C -/- filaments display a distinct 43 nm periodicity. Fourier transforms of electron microscope images typically show helical layer lines to the sixth layer line, confirming the well-ordered arrangement of the cross-bridges in both sets of filaments. However, the "forbidden" meridional reflections, thought to derive from a perturbation from helical symmetry in the wild-type filament, are weaker or absent in the transforms of the cMyBP-C -+- myocardial thick filaments. In addition, the cross-bridge array in the absence of cMyBP-C appears more easily disordered.

AB - Mutations in the thick filament associated protein cardiac myosin binding protein-C (cMyBP-C) are a major cause of familial hypertrophic cardiomyopathy. Although cMyBP-C is thought to play both a structural and a regulatory role in the contraction of cardiac muscle, detailed information about the role of this protein in stability of the thick filament and maintenance of the ordered helical arrangement of the myosin cross-bridges is limited. To address these questions, the structure of myosin thick filaments isolated from the hearts of wild-type mice containing cMyBP-C (cMyBP-C +/+) were compared to those of cMyBP-C knockout mice lacking this protein (cMyBp-C -/-). The filaments from the knockout mice hearts lacking cMyBP-C are stable and similar in length and appearance to filaments from the wild-type mice hearts containing cMyBP-C. Both wild-type and many of the cMyBP-C -/- filaments display a distinct 43 nm periodicity. Fourier transforms of electron microscope images typically show helical layer lines to the sixth layer line, confirming the well-ordered arrangement of the cross-bridges in both sets of filaments. However, the "forbidden" meridional reflections, thought to derive from a perturbation from helical symmetry in the wild-type filament, are weaker or absent in the transforms of the cMyBP-C -+- myocardial thick filaments. In addition, the cross-bridge array in the absence of cMyBP-C appears more easily disordered.

UR - http://www.scopus.com/inward/record.url?scp=41449090449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41449090449&partnerID=8YFLogxK

U2 - 10.1529/biophysj.107.115899

DO - 10.1529/biophysj.107.115899

M3 - Article

VL - 94

SP - 1707

EP - 1718

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 5

ER -