Kavli Affiliate: Stanislas Leibler
| Authors: Pablo Sartori and Stanislas Leibler
| Summary:
One of the tenets of molecular biology is that dynamical transitions between three dimensional structures largely determine the function of individual proteins, as well as multi-protein assemblies. Therefore, it seems only natural that evolutionary analysis of proteins, presently based mainly on their primary sequence, needs to shift its focus towards their function as assessed by corresponding structural transitions. This can been facilitated by recent progress in cryogenic electron microscopy that provides atomic structures of multiple conformational states for multi-protein assemblies isolated from evolutionarily related species. In this work, we study evolutionary conservation of (multi)protein function by using mechanical strain as a quantitative footprint of structural transitions. We adopt the formalism of finite strain analysis, developed in condensed matter physics and engineering, and apply it, as a case study, to a classical multi-protein assembly, the ATP synthase. Our Protein Strain Analysis (PSA) provides a precise characterization of rotation domains that agrees with the present biophysical knowledge. In addition, we obtain a strain distribution on the protein structure associated with functional transitions. By analyzing in detail the strain patterns of the β chains responsible for ATP synthesis across different species, we show that they are evolutionarily conserved for the same functional transition. Such conservation is not revealed by displacement or rotation patterns. Furthermore, within each functional transition, we are able to identify conserved strain patterns for ATP synthases isolated from different organisms. Our results promote strain as an important quantity close to protein function, which is independent of structural alignments and coordinate systems. The observed strain conservation across evolutionary distant species indicates that this quantity should be essential in future structure-based evolutionary studies of protein (and multi-protein assembly) function.