Professor Tatyana Polenova, University of Delaware

“Structure and Dynamics of Microtubule-Associated and HIV-1 Protein Assemblies by Magic Angle Spinning NMR Spectroscopy”

About the Seminar

Microtubules (MTs) and their associated proteins (MAPs) play important roles in vesicle and organelle transport, cell motility and cell division. Dynactin multisubunit assembly is the activator of the cytoplasmic microtubule-based dynein retrograde motor complex. CAP-Gly microtubule binding domain of dynactin's p150Glued subunit is critical for the regulation of dynein's motility. Mutations in the CAP-Gly domain are associated with neurological disorders, but the mechanism by which the CAP-Gly domain recognizes microtubules remains largely unknown, particularly at the atomic level. I will present the 3D structures of CAP-Gly free and assembled on microtubules, determined by magic angle spinning (MAS) NMR. I will discuss the insights gained into structural and dynamic basis of CAP-Gly’s biological function and interaction with its binding partners and microtubules.

HIV-1 capsid proteins (CA) assemble into cone-like structures and enclose the viral RNA genome together with a small complement of proteins during viral maturation. CA exhibits structural polymorphism and can assemble into various morphologies, such as cones, tubes, and spheres. I will present our recent investigations into the structure and dynamics of CA assemblies and their complexes with a host cell protein cyclophilin A.

To study the above assemblies, we have focused our efforts on establishing NMR methodologies that overcome sensitivity and resolution challenges.  An overview of these methods will be presented.

About the Speaker

Tatyana Polenova is a Professor of Chemistry and Biochemistry and the Director of an NIH Center of Biomedical Research Excellence (NIH-COBRE, “Molecular Design of Advanced Biomaterials”) at the University of Delaware. She received her B.S. degree (diploma with excellence) from Moscow State University in Russian Federation in 1992. She received M. A., M. Phil., and Ph.D. degrees from Columbia University (with Professor Ann McDermott) in 1994, 1996, and 1997, respectively. She continued as a postdoctoral researcher at Columbia University (with Professor Ann McDermott) in 1997-1999. In 1999, she joined the chemistry and biochemistry faculty of CUNY-Hunter College as an assistant professor in 1999, and then relocated to Newark, Delaware, to join the chemistry and biochemistry faculty of the University of Delaware in 2003. She was promoted to an associate professor in 2006, and to full professor in 2012. Her research interests are interdisciplinary and focus on understanding structure, dynamics and function of complex macromolecular assemblies, biological tissues and inorganic materials in the solid state. The major experimental tool used in the Polenova laboratory is NMR spectroscopy combined with computational quantum-mechanical and biophysical methods. Biomolecular solid-state NMR spectroscopy has emerged as an integral structural biology tool due to its unique capability to yield atomic-level information in insoluble macroscopically disordered systems, such as biological assemblies, membrane proteins, and fibrils. Of particular interest to the Polenova group are systems where solid-state NMR methods provide unique (and often the only) insight into structure and dynamics: i) physiologically important microtubule/cargo protein assemblies whose malfunction is associated with multiple diseases; ii) HIV-1 capsid protein assemblies whose function is important in the virus pathogenicity; iii) biotechnologically important vanadium haloperoxidases; iv) intervertebral disc tissues whose aging and damage cause the prevalent degenerative disc disease; v) technologically relevant oxoanionic solids. Understanding structure, dynamics and function of these complex systems is critical for design of novel therapeutic strategies and diagnostic methods. Her work combines fundamental investigations in structural biology and biophysics with applied biomedical research seeking to develop novel magnetic-resonance-based diagnostic methods. Much of the research involves development of new solid-state NMR methods. Tatyana Polenova was the recipient of the Miller Award for Outstanding Teaching (Columbia University, 2004), NSF-CAREER Award (2003), and the Young Investigator Presentation Award (the 5th International Symposium on Chemistry and Biological Chemistry of Vanadium, 2006). She was an Erasmus Mundus Scholar and Visiting Professor at the University of Lille (Lille, France, 2012), a Visiting Professor at ENS and CNRS-Lyon (Lyon, France, 2014), a John van Geuns Lecturer at the University of Amsterdam (Amsterdam, The Netherlands, 2010), and the Varian Lecturer at the University of Ottawa (Ottawa, Canada, 2005). She served as the Chair of the 55th Experimental Nuclear Magnetic Resonance Conference (ENC) held in 2014. She is a section editor of eMagRes (formerly Encyclopedia of Magnetic Resonance), an editorial board member of Journal of Biomolecular NMR, a member of ACS Joint Board-Council Committee on Publications (JBCCP), a member of the Franklin Institute Committee of Science and Arts. She currently serves on the executive committee of the Experimental Nuclear Magnetic Resonance Conference (ENC), on the scientific committee of Rocky Mountain Conference on Magnetic Resonance, and on the board of the Eastern Analytical Symposium.