Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function

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Standard

Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function. / Chan, Chun; Fan, Jun; Messer, Andrew E.; Marston, Steve B.; Iwamoto, Hiroyuki; Ochala, Julien.

I: Biochimica et Biophysica Acta - Molecular Basis of Disease, Bind 1862, Nr. 8, 01.08.2016, s. 1453-1458.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Chan, C, Fan, J, Messer, AE, Marston, SB, Iwamoto, H & Ochala, J 2016, 'Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function', Biochimica et Biophysica Acta - Molecular Basis of Disease, bind 1862, nr. 8, s. 1453-1458. https://doi.org/10.1016/j.bbadis.2016.04.013

APA

Chan, C., Fan, J., Messer, A. E., Marston, S. B., Iwamoto, H., & Ochala, J. (2016). Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1862(8), 1453-1458. https://doi.org/10.1016/j.bbadis.2016.04.013

Vancouver

Chan C, Fan J, Messer AE, Marston SB, Iwamoto H, Ochala J. Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function. Biochimica et Biophysica Acta - Molecular Basis of Disease. 2016 aug. 1;1862(8):1453-1458. https://doi.org/10.1016/j.bbadis.2016.04.013

Author

Chan, Chun ; Fan, Jun ; Messer, Andrew E. ; Marston, Steve B. ; Iwamoto, Hiroyuki ; Ochala, Julien. / Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function. I: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2016 ; Bind 1862, Nr. 8. s. 1453-1458.

Bibtex

@article{98d49b9a51e34bf488c50c766104f4af,
title = "Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function",
abstract = "In humans, more than 200 missense mutations have been identified in the ACTA1 gene. The exact molecular mechanisms by which, these particular mutations become toxic and lead to muscle weakness and myopathies remain obscure. To address this, here, we performed a molecular dynamics simulation, and we used a broad range of biophysical assays to determine how the lethal and myopathy-related H40Y amino acid substitution in actin affects the structure, stability, and function of this protein. Interestingly, our results showed that H40Y severely disrupts the DNase I-binding-loop structure and actin filaments. In addition, we observed that normal and mutant actin monomers are likely to form distinctive homopolymers, with mutant filaments being very stiff, and not supporting proper myosin binding. These phenomena underlie the toxicity of H40Y and may be considered as important triggering factors for the contractile dysfunction, muscle weakness and disease phenotype seen in patients.",
keywords = "Actin, Contractile dysfunction, In vitro motility assay, Molecular dynamics, Myopathy, Small-angle X-ray scattering",
author = "Chun Chan and Jun Fan and Messer, {Andrew E.} and Marston, {Steve B.} and Hiroyuki Iwamoto and Julien Ochala",
year = "2016",
month = aug,
day = "1",
doi = "10.1016/j.bbadis.2016.04.013",
language = "English",
volume = "1862",
pages = "1453--1458",
journal = "B B A - Molecular Basis of Disease",
issn = "0925-4439",
publisher = "Elsevier",
number = "8",

}

RIS

TY - JOUR

T1 - Myopathy-inducing mutation H40Y in ACTA1 hampers actin filament structure and function

AU - Chan, Chun

AU - Fan, Jun

AU - Messer, Andrew E.

AU - Marston, Steve B.

AU - Iwamoto, Hiroyuki

AU - Ochala, Julien

PY - 2016/8/1

Y1 - 2016/8/1

N2 - In humans, more than 200 missense mutations have been identified in the ACTA1 gene. The exact molecular mechanisms by which, these particular mutations become toxic and lead to muscle weakness and myopathies remain obscure. To address this, here, we performed a molecular dynamics simulation, and we used a broad range of biophysical assays to determine how the lethal and myopathy-related H40Y amino acid substitution in actin affects the structure, stability, and function of this protein. Interestingly, our results showed that H40Y severely disrupts the DNase I-binding-loop structure and actin filaments. In addition, we observed that normal and mutant actin monomers are likely to form distinctive homopolymers, with mutant filaments being very stiff, and not supporting proper myosin binding. These phenomena underlie the toxicity of H40Y and may be considered as important triggering factors for the contractile dysfunction, muscle weakness and disease phenotype seen in patients.

AB - In humans, more than 200 missense mutations have been identified in the ACTA1 gene. The exact molecular mechanisms by which, these particular mutations become toxic and lead to muscle weakness and myopathies remain obscure. To address this, here, we performed a molecular dynamics simulation, and we used a broad range of biophysical assays to determine how the lethal and myopathy-related H40Y amino acid substitution in actin affects the structure, stability, and function of this protein. Interestingly, our results showed that H40Y severely disrupts the DNase I-binding-loop structure and actin filaments. In addition, we observed that normal and mutant actin monomers are likely to form distinctive homopolymers, with mutant filaments being very stiff, and not supporting proper myosin binding. These phenomena underlie the toxicity of H40Y and may be considered as important triggering factors for the contractile dysfunction, muscle weakness and disease phenotype seen in patients.

KW - Actin

KW - Contractile dysfunction

KW - In vitro motility assay

KW - Molecular dynamics

KW - Myopathy

KW - Small-angle X-ray scattering

UR - http://www.scopus.com/inward/record.url?scp=84971351198&partnerID=8YFLogxK

U2 - 10.1016/j.bbadis.2016.04.013

DO - 10.1016/j.bbadis.2016.04.013

M3 - Journal article

AN - SCOPUS:84971351198

VL - 1862

SP - 1453

EP - 1458

JO - B B A - Molecular Basis of Disease

JF - B B A - Molecular Basis of Disease

SN - 0925-4439

IS - 8

ER -

ID: 245662509