The Hidden Power of Molecular Symmetry in Crafting the Blueprint of Life

Nature has a peculiar way of assembling some of its most complex creations. From bacterial cell surfaces and other microorganisms to virus capsids, symmetry reigns supreme. The formation of these accurate patterns is not only beautiful and awe-inspiring but also fundamental to the functionality of natural accretions. However, the process of understanding the structural organization of such symmetrical assemblies has remained a scientific mystery—until now.

SymProFold is a novel pipeline that predicts the structural organization of symmetrical biological assemblies from protein sequences only. From the S-layer lattices that serve as defensive structures surrounding bacterial cells to the viral capsids that envelope the genetic material, SymProFold offers a new perspective on solving these biological jigsaw puzzles.

Figure 1. Top view of the S-layers

Self-assembly is a bit more complicated and this is the driving force for most of the symmetry that is seen in biological systems. Imagine that these individual proteins are independently assembling and self-organizing into large complex and highly ordered multifaceted structures. These symmetrical patterns are therefore not just fancy designs but perform such fundamental shafts as cell protection, environmental adaptation, and immunity. Nevertheless, using experimental techniques to solve structures of such proteins is a challenging task due to the diverse sequence of the proteins that form them.

Figure 2. General workflow of SymProFold

That is where SymProFold comes into play, utilizing the reliability of the AlphaFold-Multimer predictions. Using all the known mirror-symmetry operations, namely p1, p2, p3, p4, and p6, it determines which is most probable to be present in every assembly. From there, the pipeline builds models that are further tested against the experimental data. The innovation of SymProFold lies in its capacity to deliver high-accuracy structural predictions for sequences, with minimal or no reliance on experimental information, opening up new avenues for research in nanotechnology, medicine as well as environmental science.

Protein symmetry is not only relevant to structure stability but also to their functions, which in turn gives an understanding of the way these proteins relate to their surroundings. Thus, stressing the structural aspect of protein organization into symmetrical assemblies, SymProFold paves the way for the design of numerous new uses in the sphere of biotechnology. It will be fascinating to think of controlled drug delivery systems designed from S-layer proteins or viral capsids to fight infections. Utilizing and exploring SymProFold is not only useful for early mapping and analysis but is also a toehold into the concepts of molecular design and a glance at the future of biology and technology.

 

References:

Buhlheller C, Sagmeister T, Grininger C, Gubensäk N, Sleytr UB, Usón I, et al. SymProFold: Structural prediction of symmetrical biological assemblies. Nat Commun 15, 8152 (2024). https://doi.org/10.1038/s41467-024-52138-3  

Image Credits:

Cover Image - https://www.harvardmagazine.com/2023/08/montage-developmental-biology

Figure 1 - https://www.nature.com/articles/s41467-024-52138-3/figures/3

Figure 2 - https://www.nature.com/articles/s41467-024-52138-3/figures/1