Molecular dynamics simulations and single molecule experiments are used to suggest that charged helices in the medial tail domain participate in myosin VI dimerization (Kim et al., 2010), which reinforces the mechanism that unfolding of the three helix bundle in the proximal tail serves as a lever arm extension.
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http://dx.doi.org/10.1016/j.str.2010.10.004 | DOI Listing |
Int J Mol Sci
December 2024
Research Center of Biotechnology, A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow 119071, Russia.
Pediatric dilated cardiomyopathy (DCM) is a rare heart muscle disorder leading to the enlargement of all chambers and systolic dysfunction. We identified a novel de novo variant, c.88A>G (p.
View Article and Find Full Text PDFGenetics
November 2024
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD, 21205 USA.
Myosin storage myopathy (MSM) is a rare skeletal muscle disorder caused by mutations in the slow muscle/β-cardiac myosin heavy chain (MHC) gene. MSM missense mutations frequently disrupt the tail's stabilizing heptad repeat motif. Disease hallmarks include subsarcolemmal hyaline-like β-MHC aggregates, muscle weakness and, occasionally, cardiomyopathy.
View Article and Find Full Text PDFPNAS Nexus
August 2024
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, 500 University Dr, Hershey, PA 17033, USA.
Inherited mutations in human beta-cardiac myosin (M2β) can lead to severe forms of heart failure. The E525K mutation in M2β is associated with dilated cardiomyopathy (DCM) and was found to stabilize the interacting heads motif (IHM) and autoinhibited super-relaxed (SRX) state in dimeric heavy meromyosin. However, in monomeric M2β subfragment 1 (S1) we found that E525K enhances (threefold) the maximum steady-state actin-activated ATPase activity ( ) and decreases (eightfold) the actin concentration at which ATPase is one-half maximal ( ).
View Article and Find Full Text PDFMolecules
June 2024
Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Gangwon, Republic of Korea.
Actin, which plays a crucial role in cellular structure and function, interacts with various binding proteins, notably myosin. In mammals, actin is composed of six isoforms that exhibit high levels of sequence conservation and structural similarity overall. As a result, the selection of actin isoforms was considered unimportant in structural studies of their binding with myosin.
View Article and Find Full Text PDFPediatr Nephrol
October 2024
Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Background: Steroid-resistant nephrotic syndrome is the second leading cause of chronic kidney disease among patients < 25 years of age. Through exome sequencing, identification of > 65 monogenic causes has revealed insights into disease mechanisms of nephrotic syndrome (NS).
Methods: To elucidate novel monogenic causes of NS, we combined homozygosity mapping with exome sequencing in a worldwide cohort of 1649 pediatric patients with NS.
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