Bioinformatic studies of small disulphide-rich proteins (SDPs)

Abstract

Small disulfide-rich proteins (SDPs) include many secretory proteins which serve predatory, defensive or regulatory roles (such as toxins, inhibitors and hormones), and they are rich source for therapeutic drugs. Disulphide bridges play crucial roles in the 3D structure, function and evolution of SDPs. The roles and patterns of disulphide bridges in SDPs were investigated using bioinformatic approaches. The systematic analyses suggested that cysteine signature can facilitate the detection of distantly related homologs or convergently evolved structures. Based on the rules derived from the analyses, a software pipeline were designed and implemented specifically for the automated comparative modeling of SDPs. A specific family of SDPs, potato type II proteinase inhibitor family (Pot II) was studied. The comprehensive analyses of Pot II family characterized the conserved patterns in 3D structure, protein sequence and gene structure. The analysis suggested heterogeneous selection pressure at different regions within the Pot II domains. As opposed to purifying selection over the cysteine scaffold that is expected, some evidence for positive selection on the reactive site is presented, illustrating the power and utility of bioinformatics tools in the study of SDPs.