New Greenberg lab publication

In collaboration with the Leinwand and Bowman labs, we show that the dynamics of myosin play a critical role in determining drug specificity.  The paper can be found here.  Congratulations to all of the authors.
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New Greenberg lab preprint looking at how the cardiac myosin working stroke is modulated by the thin filament

Human heart contraction is powered by the molecular motor β-cardiac myosin, which pulls on thin filaments consisting of actin and the regulatory proteins troponin and tropomyosin. In some muscle and non-muscle systems, these regulatory proteins tune the kinetics, mechanics, and load dependence of the myosin working stroke. Despite having a central role in health and disease, it is not well understood whether the mechanics or kinetics of β-cardiac myosin are affected by regulatory proteins. We show that regulatory proteins do not affect the mechanics or load-dependent kinetics of the working stroke at physiologically relevant ATP concentrations; however, they can affect the kinetics at low ATP concentrations, suggesting a mechanism beyond simple steric blocking. This has important implications for modeling of cardiac physiology and diseases. Paper can be found here.
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New collaborative preprint between the Greenberg, Bowman, and Leinwand labs examining the how drugs target specific myosin isoforms.

Specific myosin isoforms have emerged as drug targets in diseases including heart failure, cancer, muscle diseases, and parasitic infections; however, targeting specific myosins without affecting others has been challenging since most myosins share a common structure.  Here, we show that the structural dynamics play a critical role in determining drug specificity. The understandings gleaned from this study will help with the design of new therapeutics targeting specific myosin isoforms. To read the paper, click here.
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New Greenberg lab collaborative publication on tropomyosin mutations in myopathies and birth defects

In collaboration with the Gurnett and Johnson labs, we looked at pathogenic mutations in tropomyosin that cause various forms of skeletal myopathies and birth defects. McAdow J, Yang S, Ou T, Huang G, Dobbs MB, Gurnett CA, Greenberg MJ, Johnson AN. A pathogenic mechanism associated with myopathies and structural birth defects involves TPM2 directed myogenesis. JCI Insight. 2022 May 17:e152466. doi: 10.1172/jci.insight.152466. Epub ahead of print. PMID: 35579956.
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Greenberg lab and friends present at BPS 2022

The Greenberg lab had 4 presentations at BPS 2022: Platform (Samantha Barrick - Postdoc): STRUCTURAL DIFFERENCES IN VINCULIN AND METAVINCULIN ACTIN-BINDING DOMAINS EXPLORED BY MOLECULAR DYNAMICS SIMULATIONS Poster (Jeff Lotthammer – Student Bowman lab): EXPLORING THE MYOSIN ACTIVE/AUTO-INHIBITED STATE EQUILIBRIUM BY MARKOV STATE MODELING Poster (Artur Meller – Student Bowman lab): SIGNATURES OF ALLOSTERIC MODULATOR SPECIFICITY ARE ENCODED IN MYOSIN MOTOR DOMAIN EQUILIBRIUM FLUCTUATIONS Poster (Michael Greenberg - PI): HARNESSING MULTISCALE MODELS OF A DILATED CARDIOMYOPATHY MUTATION FOR PRECISION MEDICINE
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Greenberg lab presents at ASCB 2021

The Greenberg lab had 2 posters as ASCB 2021: Dr. Samantha Barrick presented a poster: A Troponin T Variant Linked with Pediatric Dilated Cardiomyopathy Decreases Cardiac Contractility by Reducing the Coupling of Thin Filament Activation to Myosin and Calcium Binding And Michael Greenberg presented: Utilizing Multiscale Models of a Dilated Cardiomyopathy Mutation for Precision Medicine, which included collaborative work from the Lavine lab.
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