I’ve been watching Olympic gymnastics which has me thinking about flexibility which has me thinking about the most inflexible amino acid (protein letter), Proline – which has me thinking about how Jason McClellan and his lab figured out how to use prolines to stabilize coronavirus Spike proteins, enabling research on it and the production of effective vaccines to guard against COVID-19. 



No new text today because now I need to get back to work and not just do cartwheels down the hall… But here are some links for more…

For more information about Spike (and figures), see this past post: https://bit.ly/coronavirusspike 

For more information about proline (whose friends call it Pro or P), see this past post: http://bit.ly/prolinestuff 

Here are a few key papers from Jason McClellan and his lab at the University of Texas, Austin:

Here is where they figure out the 2 Proline trick to stabilize a Spike protein from the MERS MERS: 

Immunogenicity and structures of prefusion MERS S

Jesper Pallesen, Nianshuang Wang, Kizzmekia S. Corbett, Daniel Wrapp, Robert N. Kirchdoerfer, Hannah L. Turner, Christopher A. Cottrell, Michelle M. Becker, Lingshu Wang, Wei Shi, Wing-Pui Kong, Erica L. Andres, Arminja N. Kettenbach, Mark R. Denison, James D. Chappell, Barney S. Graham, Andrew B. Ward, Jason S. McLellan

Proceedings of the National Academy of Sciences Aug 2017, 114 (35) E7348-E7357; DOI: 10.1073/pnas.1707304114

https://doi.org/10.1073/pnas.1707304114

Here’s where they use that 2 Proline trick to get a cryo-EM structure of Spike (figure out what it looks like) only like a month after knowing its sequence:

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

BY DANIEL WRAPP, NIANSHUANG WANG, KIZZMEKIA S. CORBETT, JORY A. GOLDSMITH, CHING-LIN HSIEH, OLUBUKOLA ABIONA, BARNEY S. GRAHAM, JASON S. MCLELLAN

SCIENCE13 MAR 2020 : 1260-1263 https://science.sciencemag.org/content/367/6483/1260 

Here’s where they introduce more prolines to make HexaPro:

Structure-based design of prefusion-stabilized SARS-CoV-2 spikes

BY CHING-LIN HSIEH, JORY A. GOLDSMITH, JEFFREY M. SCHAUB, ANDREA M. DIVENERE, HUNG-CHE KUO, KAMYAB JAVANMARDI, KEVIN C. LE, DANIEL WRAPP, ALISON G. LEE, YUTONG LIU, CHIA-WEI CHOU, PATRICK O. BYRNE, CHRISTY K. HJORTH, NICOLE V. JOHNSON, JOHN LUDES-MEYERS, ANNALEE W. NGUYEN, JUYEON PARK, NIANSHUANG WANG, DZIFA AMENGOR, JASON J. LAVINDER, GREGORY C. IPPOLITO, JENNIFER A. MAYNARD, ILYA J. FINKELSTEIN, JASON S. MCLELLAN

SCIENCE18 SEP 2020 : 1501-1505 https://science.sciencemag.org/content/369/6510/1501 

Here’s a great talk by Jason McClellan: https://youtu.be/EH2QIxmZIWA 

the paper with some of the structures in one of my figures: Distinct conformational states of SARS-CoV-2 spike protein BY YONGFEI CAI, JUN ZHANG, TIANSHU XIAO, HANQIN PENG, SARAH M. STERLING, RICHARD M. WALSH JR., SHAUN RAWSON, SOPHIA RITS-VOLLOCH, BING CHEN SCIENCE25 SEP 2020 : 1586-1592 https://science.sciencemag.org/content/369/6511/1586


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