About the Seminar:

Many viruses that cause human disease are enveloped by a membrane obtained during budding from an infected host cell. Example virus families are HIV, influenza, and coronaviruses. Infection of new cells requires joining (“fusion”) of viral and cellular membranes. Fusion is catalyzed by glycoprotein subunits that are part of the spikes that protrude from the virus. Although subunits from different virus families share a common fusion function, they not have similar amino acid sequences. A major goal of the Weliky group is understanding how these subunits catalyze fusion. This new understanding should aid development of anti-viral therapeutics and universal vaccines. NMR is an important technique for this understanding, in particular for determining structures and motions of fusion subunit and lipid molecules in membranes. One way a fusion subunit may catalyze fusion is by inducing lipid motions along the fusion pathway. For example, lipid protrusion out of the membrane accelerates joining of outer leaflets of the viral and cellular membranes which is an initial step in fusion. We showed by NMR that protrusion probability is increased ~10 for lipids next to the fusion peptide (Fp) segment of the influenza fusion subunit. One fairly-unexplored strength of solid-state NMR is determination of populations of distinct molecular structures when the chemical shifts of the different structures are unresolved. We have done such determination for intermolecular registries (alignments) of adjacent molecules in antiparallel beta sheets of the membrane-bound Fp of the HIV fusion subunit. Global analysis of the NMR data reveals >10 populated registries which to our knowledge is unprecedented in molecular structure. HIV is a chronic infection in which the virus evades the immune system by mutation while continuing to fuse with and infect cells. A broad distribution of Fp beta sheet registries, many of which are fusion-active, is an evolutionary solution. Viruses with Fp mutations remain viable in fusion because the mutations only result in shifts in populations among different functional registries.

About the Speaker:

David Weliky grew up for the most part in New Jersey and received a B.A. with High Honors in Chemistry and Physics from Swarthmore College. David worked at Aerospace Corporation and subsequently received a Ph.D. in Chemistry from University of Chicago working with Takeshi Oka and doing research on infrared spectroscopy of deuterium impurity molecules in crystalline molecular hydrogen solid. At Chicago, David was a NSF Pre-doctoral Fellow and an AT&T Ph.D. Scholar and did research for a summer with Rob Tycko at AT&T. David then worked as a post-doc with Rob at NIH and developed solid-state NMR methods to determine molecular structure and also determined the secondary structure of a peptide epitope bound to a neutralizing antibody. David’s independent career has been at Michigan State University where he is currently a Professor of Chemistry. David’s research has focused on fusion subunits of spike proteins of enveloped viruses, recombinant proteins in bacterial inclusion bodies, and high-temperature NMR of phosphochalcogenides.