Comparitive seqeunce and structural analysis of filament forming actin homologs in prokaryotes

Abstract

The actin fold is highly conserved in eukaryotes, whereas it is diverged in homologs with less than 15 per cent sequence identity and specialised for different functions in prokaryotes. Despite sharing the common actin fold, monomers differ in the architecture of their filament structures. Canonical actin and crenactin are right-handed, parallel and staggered. MreB forms antiparallel, non-helical short filaments. FtsA is single-stranded, and MamK is parallel, juxtaposed, and right-handed. ParMs and AlfA form left-handed parallel staggered filaments. My thesis addresses the question of which differences among monomer structures lead to the variety of filament architectures in the ALP family. We developed a pipeline to analyse structural variation from actin and conservation of residues across ALP families. We performed contact analysis along the longitudinal and latitudinal interfaces across protofilament. Our study reveals that the intraprotofilament interface is more conserved across ALPs, whereas the interprotofilament interface is more variable, leading to different filament variations. Variable regions like the D-loop at SD2- and the hydrophobic plug at SD4 are found to be structurally variable across ALP families, which contribute significantly to the variability observed.