Myopathy-causing Q147P TPM2 mutation shifts tropomyosin strands further towards the open position and increases the proportion of strong-binding cross-bridges during the ATPase cycle

Standard

Myopathy-causing Q147P TPM2 mutation shifts tropomyosin strands further towards the open position and increases the proportion of strong-binding cross-bridges during the ATPase cycle. / Karpicheva, O. E.; Simonyan, A. O.; Kuleva, N. V.; Redwood, C. S.; Borovikov, Y. S.

In: Biochimica et Biophysica Acta - Proteins and Proteomics, Vol. 1864, No. 3, 2016, p. 260-267.

Research output: Contribution to journal › Article

BibTeX

@article{2ce99f801ff840e1b6d0dbb255fd42ac,

title = "Myopathy-causing Q147P TPM2 mutation shifts tropomyosin strands further towards the open position and increases the proportion of strong-binding cross-bridges during the ATPase cycle",

abstract = "The molecular mechanisms of skeletal muscle dysfunction in congenital myopathies remain unclear. The present study examines the effect of a myopathy-causing mutation Q147P in β-tropomyosin on the position of tropomyosin on troponin-free filaments and on the actin–myosin interaction at different stages of the ATP hydrolysis cycle using the technique of polarized fluorimetry. Wild-type and Q147P recombinant tropomyosins, actin, and myosin subfragment-1 were modified by 5-IAF, 1,5-IAEDANS or FITC-phalloidin, and 1,5-IAEDANS, respectively, and incorporated into single ghost muscle fibers, containing predominantly actin filaments which were free of troponin and tropomyosin. Despite its reduced affinity for actin in co-sedimentation assay, the Q147P mutant incorporates into the muscle fiber. However, compared to wild-type tropomyosin, it locates closer to the center of the actin filament. The mutant tropomyosin increases the proportion of the strong-binding myosin heads and disrupts the co-operation of actin and my",

keywords = "β-Tropomyosin, Actin, Myosin head, Ghost muscle fiber, Congenital myopathy, Polarized fluorescence",

author = "Karpicheva, {O. E.} and Simonyan, {A. O.} and Kuleva, {N. V.} and Redwood, {C. S.} and Borovikov, {Y. S.}",

year = "2016",

doi = "10.1016/j.bbapap.2015.12.004",

language = "English",

volume = "1864",

pages = "260--267",

journal = "Biochimica et Biophysica Acta - Proteins and Proteomics",

issn = "1570-9639",

publisher = "Elsevier",

number = "3",

}

RIS

TY - JOUR

T1 - Myopathy-causing Q147P TPM2 mutation shifts tropomyosin strands further towards the open position and increases the proportion of strong-binding cross-bridges during the ATPase cycle

AU - Karpicheva, O. E.

AU - Simonyan, A. O.

AU - Kuleva, N. V.

AU - Redwood, C. S.

AU - Borovikov, Y. S.

PY - 2016

Y1 - 2016

N2 - The molecular mechanisms of skeletal muscle dysfunction in congenital myopathies remain unclear. The present study examines the effect of a myopathy-causing mutation Q147P in β-tropomyosin on the position of tropomyosin on troponin-free filaments and on the actin–myosin interaction at different stages of the ATP hydrolysis cycle using the technique of polarized fluorimetry. Wild-type and Q147P recombinant tropomyosins, actin, and myosin subfragment-1 were modified by 5-IAF, 1,5-IAEDANS or FITC-phalloidin, and 1,5-IAEDANS, respectively, and incorporated into single ghost muscle fibers, containing predominantly actin filaments which were free of troponin and tropomyosin. Despite its reduced affinity for actin in co-sedimentation assay, the Q147P mutant incorporates into the muscle fiber. However, compared to wild-type tropomyosin, it locates closer to the center of the actin filament. The mutant tropomyosin increases the proportion of the strong-binding myosin heads and disrupts the co-operation of actin and my

AB - The molecular mechanisms of skeletal muscle dysfunction in congenital myopathies remain unclear. The present study examines the effect of a myopathy-causing mutation Q147P in β-tropomyosin on the position of tropomyosin on troponin-free filaments and on the actin–myosin interaction at different stages of the ATP hydrolysis cycle using the technique of polarized fluorimetry. Wild-type and Q147P recombinant tropomyosins, actin, and myosin subfragment-1 were modified by 5-IAF, 1,5-IAEDANS or FITC-phalloidin, and 1,5-IAEDANS, respectively, and incorporated into single ghost muscle fibers, containing predominantly actin filaments which were free of troponin and tropomyosin. Despite its reduced affinity for actin in co-sedimentation assay, the Q147P mutant incorporates into the muscle fiber. However, compared to wild-type tropomyosin, it locates closer to the center of the actin filament. The mutant tropomyosin increases the proportion of the strong-binding myosin heads and disrupts the co-operation of actin and my

KW - β-Tropomyosin

KW - Actin

KW - Myosin head

KW - Ghost muscle fiber

KW - Congenital myopathy

KW - Polarized fluorescence

U2 - 10.1016/j.bbapap.2015.12.004

DO - 10.1016/j.bbapap.2015.12.004

M3 - Article

VL - 1864

SP - 260

EP - 267

JO - Biochimica et Biophysica Acta - Proteins and Proteomics

JF - Biochimica et Biophysica Acta - Proteins and Proteomics

SN - 1570-9639

IS - 3

ER -

ID: 7603885