Our next speaker will be Professor Angela Gronenborn, Head of the Department of Structural Biology (School of Medicine, University of Pittsburgh) and Director of the Pittsburgh Center for HIV Protein Interactions.
She will talk about: “Synergy between NMR, cryo-EM and large-scale MD simulations: an all atom model of a native HIV capsid”.
Angela Gronenborn is an internationally renowned specialist in the application of nuclear magnetic resonance (NMR) spectroscopy for investigating structure, dynamics and folding of biological macromolecules. Her research harnesses the power of NMR combined with biophysics, biochemistry, and chemistry to investigate cellular processes at the molecular and atomic levels in relation to human disease. Angela Gronenborn’s group presently focuses on two areas in biology: gene regulation and HIV pathogenesis.
Prof. Gronenborn will give her talk twice:
- at EPFL, on Thursday May 19th, 2016 – Room SV 1717A, 16:15
- at UNIGE, on Friday May 20th, 2016 – room 352, 13:00
To understand how biological macromolecules work and intervene with respect to activity and function, detailed knowledge of their architecture and dynamic features is required. Evaluation of the major determinants for stability and conformational specificity of normal and disease-causing forms of molecules will allow us to unravel the complex processes associated with disease.
Her group has developed new NMR methods for determining three-dimensional structures of biological macromolecules and apply these to challenging systems. Key contributions include the development of restrained molecular dynamics/simulated annealing algorithms and multidimensional, heteronuclear spectroscopy, which allowed the extension of conventional NMR methods to higher molecular weight systems. The Gronenborn group has solved solution structures of a large number of medically and biologically important proteins, including cytokines and chemokines, transcription factors and their complexes and various HIV and AIDS related proteins. Work is also carried out on protein folding and design using the model protein GB1.
More about the conference
HIV and other retroviruses use a Trojan horse style of infection, taking advantage of a cloak that shields its genome till the time is ripe to open the shield. Once HIV gets inside the cell, it takes over the cellular machinery, turning it into a factory for its own reproduction. This entails a derailment of the normal host defense pathways, rendering HIV resistant to cell-mediated destruction responses. In mature HIV-1 particles a conical-shaped capsid core encloses the viral RNA genome. Previous structural analysis of two- and three-dimensional arrays provided a molecular model of the capsid protein (CA) hexamer and revealed three interfaces in the lattice.
Using the high-resolution NMR structure of the CA C-terminal domain (CTD) dimer and in particular the unique interface identified, it was possible to reconstruct a model for a tubular assembly of CA protein that fit extremely well into the cryoEM density map. A novel CTD-CTD interface at the local three-fold axis in the cryoEM map was confirmed by mutagenesis to be essential for function.
More recently, the cryo-EM structure of the tube was solved at 8Å resolution and this cryo-EM structure allowed unambiguous modeling and refinement by large-scale molecular dynamics (MD) simulation, resulting in all-atom models for the hexamer-of-hexamer and pentamer-of-hexamer elements of spheroidal capsids.
Furthermore, the 3D structure of a native HIV-1 core was determined by cryo-electron tomography (Cryo-ET), which in combination with MD simulations permitted the construction of a realistic all-atom model for the entire capsid, based on the 3D authentic core structure.
Opening act of the conference in Lausanne:
“A structural approach to unravel isoform-specific signalling of Bcr-Abl” by Sina Reckel, Post Doc, Hantschel lab, Swiss Institute of Experimental Cancer Research, School of Life Sciences, EPFL.