Journal
SCIENCE ADVANCES
Volume 8, Issue 5, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abl7346
Keywords
-
Categories
Funding
- Australian Research Council [DE190100624]
- Westpac Foundation [WRF2020]
- NIH [R35GM133325]
- Australian Research Council Centre of Excellence in Synthetic Biology [CE200100029]
- Centre of Excellence for Innovations in Peptide and Protein Science [CE200100012]
- Australian Research Council [DE190100624] Funding Source: Australian Research Council
Ask authors/readers for more resources
This study systematically designed protein cage variants and identified molecular parameters that govern stability and flux through their pores.
Protein cages are a common architectural motif used by living organisms to compartmentalize and control biochemical reactions. While engineered protein cages have featured in the construction of nanoreactors and synthetic organelles, relatively little is known about the underlying molecular parameters that govern stability and flux through their pores. In this work, we systematically designed 24 variants of the Thermotoga maritima encapsulin cage, featuring pores of different sizes and charges. Twelve pore variants were successfully assembled and purified, including eight designs with exceptional thermal stability. While negatively charged mutations were better tolerated, we were able to form stable assemblies covering a full range of pore sizes and charges, as observed in seven new cryo-EM structures at 2.5- to 3.6-angstrom resolution. Molecular dynamics simulations and stoppedflow experiments revealed the importance of considering both pore size and charge, together with flexibility and rate-determining steps, when designing protein cages for controlling molecular flux.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available