Professors Katie Henzler-Wildman and Chad Rienstra, co-directors of the National Magnetic Resonance Facility at Madison (NMRFAM), have been awarded a grant to study coronavirus proteins of direct relevance to COVID-19. The research is funded by a National Science Foundation EArly-concept Grants for Exploratory Research (EAGER) award, and carried out in collaboration with Assistant Professor Robert Kirchdoerfer.
The research will quickly contribute new insights into the structure and function of two important SARS-coronavirus-2 proteins: nsp8 and the membrane protein M. These proteins are key participants in genetic replication, translation, assembly and budding, and could provide vital insight into critical functions in the viral life cycle.
The protein nsp8 joins with other proteins to form larger complexes necessary for the replication of genetic material and the accuracy of that replication.
Membrane protein M mediates the viral assembly and budding of new material; there is no structural data currently available for M.
The immediate goal of the research is to understand the structure and dynamics of these proteins in relation to COVID-19 and other coronaviruses. In particular, the role they play in the replication process, why that role is important, how they interact with other proteins and molecules, and how they contribute to the overall form of the virus.
“These are the core processes of a much larger machine,” said Henzler-Wildman. “We think that the conformational changes undergone by these proteins are important for this machinery to be able to function. Getting a better handle on the core functions of this family of virus will benefit our long term ability to control them.”
This research is part of an organized international effort by the NMR community to understand the structure and function of the RNA and protein structures of SARS-CoV-2. Data from NMRFAM is being made available to other research groups as quickly as possible in order to further COVID-19 and related research. This data, and that of other NMR contributors, is shared online at COVID19-NMR.
NMRFAM has a long history of supporting activities such as remote data collection, so research contributing to this project can be performed by Madison personnel and remote collaborators despite current restrictions on physical access to the facility.
The EAGER grant funds a new direction for NMRFAM and leverages new instrumentation purchased as part of the recruitment of co-director Rienstra, who joined the Department of Biochemistry in early 2020. This solid state NMR equipment allows researchers to study molecules too large for liquid state NMR and too small for Cryo-EM. It expands the range of molecules that can now be studied through NMR technology, which has broad applications for studying the structure, dynamics and interactions of small molecules across a wide range of projects.