Summary
Alpha helices can tolerate more missense mutations and indels than beta sheets. This was initially pointed out by (1) using bioinformatics analysis and corroborated by (2) using stability measurements.
Details
Beltran et al. find, using ~500k measurements across 500 domains, that stability has a greater contribution to protein fitness in beta-sheet proteins than alpha-helical proteins. (2)
Related
1.
Abrusán G, Marsh JA. Alpha Helices Are More Robust to Mutations than Beta Strands. PLOS Computational Biology. 2016;12(12):e1005242. Available from: https://doi.org/10.1371/journal.pcbi.1005242
2.
Beltran A, Jiang X, Shen Y, Lehner B. Site saturation mutagenesis of 500 human protein domains reveals the contribution of protein destabilization to genetic disease. openRxiv; 2024. Available from: https://doi.org/10.1101/2024.04.26.591310