Michael J. Rynkiewicz
|Instructor of Physiology & Biophysics
B.S. Massachusetts Institute of Technology
|Phone: (617) 358-8482
Fax: (617) 358-8758
Address: see below
Link to BU Faculty Profile
I am a protein crystallographer with extensive experience in computational structural analysis. My work over the years has encompassed a broad range of techniques, including protein crystallography, kinetic assays, organic synthesis, NMR and ultraviolet spectroscopy, small molecule structure-based drug design, epitope mapping of antibodies, and molecular dynamics calculations.
Mechanism of tropomyosin activation probed by energy landscape analysis. Muscle contraction is regulated in part by tropomyosin. The tropomysosin molecules wrap around actin thin filaments in the sarcomere, and the position of the tropomyosin chain regulates the binding of myosin to the thin filament. The regulatory transitions of tropomyosin have been mapped out by a variety of techniques including negative stain and cryo electron microscopy and computational studies. However, the electron microscopy structures only provide a static picture of tropomyosin during regulation, any dynamic information is lost. Many cardiomyopathies derive their deleterious cardiovascular effects from mutations of tropomyosin. Presumably, these mutations alter the regulatory transitions of tropomyosin in subtle ways that lead to aberrant cardiac function. By studying the energy of tropomyosin at discreet locations on the actin filament for mutant and wild-type tropomyosins, we hope to learn the root causes of these cardiomyopathies and propose mechanisms by which they develop.
The innate immune system provides a first line response to inhaled pathogens, partly through the activities of the C-type lectin proteins surfactant protein-A and surfactant protein-D. Each surfactant protein has a unique function, and our structural work was aimed at learning the molecular mechanisms by which each protein performs its function in lung surfactant. For surfactant protein-D, we studied a mutant (D325A/R343V) that displayed a broader range and increased potency of efficacy against influenza virus strains. For surfactant protein-A, we created specific mutations to the calcium binding properties of the molecule that were able to incorporate some surfactant protein-D-like activities into surfactant protein-A. These studies help to understand the structural evolution of the specific activities of the two surfactant proteins.
Rynkiewicz MJ, Wu H, Cafarella TR, Nikolaidis NM, Head JF, Seaton BA, McCormack FX. (2017) Differential Ligand Binding Specificities of the Pulmonary Collectins Are Determined by the Conformational Freedom of a Surface Loop. Biochemistry. Aug 8; 56(31):4095-4105. PMID: 28719181.
Rynkiewicz MJ, Fischer S, Lehman W. (2016) The propensity for tropomyosin twisting in the presence and absence of F-actin. Arch Biochem Biophys. 2016 Nov 1; 609:51-58. PMID: 27663225.
Goh BC, Wu H, Rynkiewicz MJ, Schulten K, Seaton BA, McCormack FX. (2016) Elucidation of Lipid Binding Sites on Lung Surfactant Protein A Using X-ray Crystallography, Mutagenesis, and Molecular Dynamics Simulations. Biochemistry. 2016 Jul 5; 55(26):3692-701. PMID: 27324153.
Fischer S, Rynkiewicz MJ, Moore JR, Lehman W. (2016) Tropomyosin diffusion over actin subunits facilitates thin filament assembly. Struct Dyn. 2016 Jan 14; 3(1):012002. PMID: 26798831.
Rynkiewicz MJ, Schott V, Orzechowski M, Lehman W, Fischer S. (2015) Electrostatic interaction map reveals a new binding position for tropomyosin on F-actin. J Muscle Res Cell Motil. 2015 Dec; 36(6):525-33. PMID: 26286845
Department of Physiology & Biophysics
Boston University School of Medicine
700 Albany St. W408D
Boston MA 02118-2526
Phone: (617) 358-8482
Fax: (617) 358-8758