Research Description
Molecular mechanisms of function and dysfunction of skeletal muscle. I am interested in the molecular mechanism of muscle contraction, particularly in the mechanism of interactions between actin and myosin. My working hypothesis is that muscle contractility results from structural transitions in actin and myosin during active interaction in the presence of ATP. Recently we have proposed – and documented in our work - that that these transitions are modulated by the essential light chains of myosin. I apply my basic research approaches to investigate molecular mechanisms of muscle dysfunction, such as the age-related or mutations-related weakening of muscle. In studies on aging, I am pursuing the hypothesis that weakening of aging muscle is associated with the oxidative modification of actin and myosin by reactive oxygen species and subsequent inhibition of biological functions. In studies on mutations, I focus on possibilities of substitution of mutated proteins by their analogues, as shown in works on the role of actin dynamics in muscular dystrophy. Recently, I am interested in expanding the knowledge and methodology of basic research to biomedical application. Using high throughput screen I am searching for a small molecules which are capable to regulate actin-myosin interaction and thus have therapeutic potential in improving function of impaired muscle.
Recent Publications
Prochniewicz E, Janson N, Thomas DD, De la Cruz EM. 2005. Cofilin increases the torsional flexibility and dynamics of actin filaments. J Mol Biol. 353: 990-1000.
Prochniewicz E, Thomas DD, Thompson LV. Age-related decline in actomyosin function. 2005. J Gerontol A Biol Sci Med Sci. 60: 425-31.
Korman VL, Anderson SE, Prochniewicz E, Titus MA, Thomas DD. 2006. Structural dynamics of the actin-myosin interface by site-directed spectroscopy. J Mol Biol. 356: 1107-17.
Prochniewicz E, Thompson LV, Thomas DD. 2007. Age-related decline in actomyosin structure and function. Exp Gerontol. 42: 931-8.
Prochniewicz E, Lowe DA, Spakowicz D, Higgins L, Oconor K, Thompson LV, Ferrington DA, Thomas DD. 2007. Functional, structural and chemical changes in myosin associated with hydrogen peroxide treatment of skeletal muscle fibers. 2008. Am J Physiol Cell Physiol. 294: 613-626
Prochniewicz, E, D Spakowicz, and DD Thomas. 2008. Changes in actin structural transitions associated with oxidative inhibition of muscle contraction. Biochemistry 47:11811-11817. PMC3253347.
Prochniewicz, E, D Henderson, JM Ervasti, and DD Thomas. 2009. Dystrophin and utrophin have distinct effects on the structural dynamics of actin. Proc Nat Acad Sci USA 106: 7822-7827.
Prochniewicz, E, HF Chin, DE Hannemann, AO Olivares, DD Thomas, and EM De La Cruz. 2009. Myosin isoform determines the conformational dynamics and cooperativity of actin filaments in the strongly bound actomyosin complex. J Mol Biol, 396:501-509. PMC2834967.
Prochniewicz, E, A Pierre, BR McCullough, HF Chin, W Cao, LP Saunders, DD Thomas, and EM De La Cruz. 2011. Actin filament dynamics in the actomyosin VI complex is regulated allosterically by calcium-calmodulin light chain. J Mol Biol 413:584-92. NIHMS326632.
Lin, AY, E Prochniewicz, DM Henderson,, B Li, JM Ervasti, and DD Thomas. 2012. Impacts of dystrophin and utrophin domains on actin structural dynamics: implications for therapeutic design. J Mol Biol 420:87-98. PMC3367031
Guhathakurta, P, E Prochniewicz, JM Muretta, and David D. Thomas. 2012. Allosteric communication in Dictyostelium myosin II. J Muscle Research Cell Motility 33:305-312. PMC3600821.
Colson, BA, IN Rybakova, E Prochniewicz, RL Moss, and DD Thomas. 2012. Cardiac myosin binding protein-C restricts intrafilament torsional dynamics of actin in a phosphorylation-dependent manner. Proc Nat Acad Sci USA 109:20437-20442. PMC3528524.
Prochniewicz, E, PG Guhathakurta and DD Thomas. 2013. Structural dynamics of actin during active interaction with myosin is determined by the essential light chain isoform. Biochemistry 52:1622−1630. PMC in process
Guhathakurta P, Prochniewicz E, Thomas DD. 2015. Amplitude of the actomyosin power stroke depends strongly on the isoform of the myosin essential light chain. Proc Natl Acad Sci U S A. 112:4660-5.