Marqusee Lab

Congrats to our current postdoc Amir on his latest publication with the Shakhnovich and Rodnina labs! Check out this thread about their really interesting study, combining all-atom simulation with experiment to reveal a protein's co-translational folding pathway at an atomistic level of detail

So thrilled to share that Susan was selected as a 2025 Protein Society Fellow!

This may inform our understanding of how proteins evolve to satisfy unique environmental constraints, such as resisting autolysis in the case of proteases. This has important implications in protein design as well

Protein energy landscapes affect not just how a protein first folds its structure, but also its functional and adaptive properties. In this work, Miriam performs a thorough biophysical characterization of how sequence changes affect the dynamics of two related proteases with different sequences

Exploring the sequence and structural determinants of the energy landscape from thermodynamically stable and kinetically trapped subtilisins: ISP1 and SbtE A protein's energy landscape, all accessible conformations, their populations, and dynamics of interconversion, is encoded in its primary sequence. While how this sequence encodes a protein's native ...

Excited to share our latest paper led by our talented former PhD student Miriam Hood

onlinelibrary.wiley.com/doi/10.1002/...

Update: Many congrats to our talented undergraduate student Joshua Morse for receiving a top poster award!!

In addition, come check out posters by Joshua Morse (T94), Darren Kahan (T82), Eva Gerber (F14), Mark Petersen (F77), Sophie Shoemaker (F89), Lynn Gu (F33), and Amir Bitran (S89)

Sophie Shoemaker will be giving a flash talk tomorrow afternoon in the "Proteins and Lipids: Fusion, Fission, Budding" session, while Eva Gerber will give a flash talk on Sunday as part of the morning "20 Amino Acids… and Beyond" session

Come check out presentations by the Marqusee lab at the 39th Protein Society Annual Symposium (@proteinsociety.bsky.social). Darren Kahan just gave an awesome talk on his work on IDPs.

Pleased to share a manuscript by our star former grad student, Sara Volz, showing the power of HDX-MS to probe folding intermediates of γD crystallin under native conditions. This approach could shed future light on cataract-linked aggregation. Thanks @alexguseman.bsky.social and the Gronenborn lab

Check it out and let us know what you think! We are really excited by the combination of HDX-MS with eVLPs as it provides an opportunity to more easily study viral fusion proteins and other membrane proteins in native-like environments with HDX-MS.
7/7

D614G shifts the equilibrium to favor the prefusion conformation while the S2' site stays disordered. This study provides, to our knowledge, the first molecular explanation for the dual evolutionary advantages of furin cleavage and D614G.
6/7

However, furin cleavage also increases the population of the open-interface trimer, potentially promoting premature S1 shedding. We propose that this trade-off drove the evolution of the D614G mutation, an early fixed mutation in SARS-CoV-2.
5/7

We find that furin cleavage at the S1/S2 site increases the disorder of the S2’ protease site, which may increase TMPRSS2 activity leading to more efficient fusion. This provides a mechanistic explanation for furin cleavage enhancing infectivity.
4/7

We show that the native, full-length spike samples the previously identified open-interface trimer conformation, and its populations and interconversion rates are sensitive to sequence variations.
3/7

We use eVLPs to display full-length SARS-CoV-2 spike, both with and without prefusion-stabilizing prolines, and then probe dynamics with HDX-MS. Our findings reveal significant changes in spike dynamics resulting from natural and engineered variants.
2/7

The Interplay of Furin Cleavage and D614G in Modulating SARS-CoV-2 Spike Protein Dynamics We report a detailed analysis of the full-length SARS-CoV-2 spike dynamics within a native-like membrane environment and variants inaccessible to studies on soluble constructs by conducting hydrogen-d...

Check out Sophie's new preprint on bioRxiv in collaboration with Magnus Hoffmann's lab where we conduct HDX-MS on SARS-CoV-2 spike proteins displayed on eVLPs to understand the dynamics of natural and engineered variants. 1/7 biorxiv.org/content/10.1...