Genealogy of an ancient protein family: the Sirtuins, a family of disordered members.

摘要: Sirtuins genes are widely distributed by evolution and have been found in eubacteria, archaea eukaryotes. While prokaryotic archeal species usually one or two sirtuin homologs, humans as well eukaryotes we multiple versions mammals this family is comprised of seven different homologous proteins being all NAD-dependent de-acylases. 3D structures human SIRT2, SIRT3, SIRT5 revealed the overall conformation conserved core domain but they were unable to give a structural information about presence very flexible dynamically disordered regions, role which still structurally functionally unclear. Recently, modeled 3D-structure SIRT1, most studied member family, that unexpectedly emerged intrinsically with its long terminal arms. Despite clear similarities catalytic cores between sirtuins little known general characteristics these proteins. The disorder SIRT1 propensity promoting molecular interactions make it important understand underlying mechanisms recognition reasonably should involve segments. mechanism recognition, turn, prerequisite for understanding any functional activity. Aim work what properties shared among members other organisms. We distribution features N- C-terminal segments organisms draw their evolutionary histories taking into account average length segments, amino acid composition, intrinsic disorder, charged stretches, putative phosphorylation sites, flexibility, GC content genes. Finally, carried out comprehensive analysis sites confirming those already experimentally 2 extending topology get feedback physiological functions cellular localization. Our results highlight majority possess number chemical physical strongly support involvement activities interaction protein molecules. also suggest how multisite provides possible supported positively negatively stretches might enhance strength specificity particular partner.