Abstract
BackgroundHSP90 proteins are essential molecular chaperones involved in signal transduction, cell cycle control, stress management, and folding, degradation, and transport of proteins. HSP90 proteins have been found in a variety of organisms suggesting that they are ancient and conserved. In this study we investigate the nuclear genomes of 32 species across all kingdoms of organisms, and all sequences available in GenBank, and address the diversity, evolution, gene structure, conservation and nomenclature of the HSP90 family of genes across all organisms.ResultsTwelve new genes and a new type HSP90C2 were identified. The chromosomal location, exon splicing, and prediction of whether they are functional copies were documented, as well as the amino acid length and molecular mass of their polypeptides. The conserved regions across all protein sequences, and signature sequences in each subfamily were determined, and a standardized nomenclature system for this gene family is presented. The proeukaryote HSP90 homologue, HTPG, exists in most Bacteria species but not in Archaea, and it evolved into three lineages (Groups A, B and C) via two gene duplication events. None of the organellar-localized HSP90s were derived from endosymbionts of early eukaryotes. Mitochondrial TRAP and endoplasmic reticulum HSP90B separately originated from the ancestors of HTPG Group A in Firmicutes-like organisms very early in the formation of the eukaryotic cell. TRAP is monophyletic and present in all Animalia and some Protista species, while HSP90B is paraphyletic and present in all eukaryotes with the exception of some Fungi species, which appear to have lost it. Both HSP90C (chloroplast HSP90C1 and location-undetermined SP90C2) and cytosolic HSP90A are monophyletic, and originated from HSP90B by independent gene duplications. HSP90C exists only in Plantae, and was duplicated into HSP90C1 and HSP90C2 isoforms in higher plants. HSP90A occurs across all eukaryotes, and duplicated into HSP90AA and HSP90AB in vertebrates. Diplomonadida was identified as the most basal organism in the eukaryote lineage.ConclusionThe present study presents the first comparative genomic study and evolutionary analysis of the HSP90 family of genes across all kingdoms of organisms. HSP90 family members underwent multiple duplications and also subsequent losses during their evolution. This study established an overall framework of information for the family of genes, which may facilitate and stimulate the study of this gene family across all organisms.
Highlights
90 kDa heat-shock protein (HSP90) proteins are essential molecular chaperones involved in signal transduction, cell cycle control, stress management, and folding, degradation, and transport of proteins
Seventeen completely conserved a.a. residues serve as markers to recognize any HSP90 family member, whereas membership into each subfamily is assigned by additional specific signature motifs, with the exception of high temperature protein G (HTPG) subfamily members
The endoplasmic reticulum (ER), a new compartment in the cell, required molecular chaperones to transmit information within the compartment and to help transport "passenger proteins" across the membranes. Because both of these functions have been associated with HSP90B members [47], we propose that the ancestral HTPG of the partner eubacteria evolved into HSP90B at the very beginning of the eukaryote cell formation
Summary
HSP90 proteins are essential molecular chaperones involved in signal transduction, cell cycle control, stress management, and folding, degradation, and transport of proteins. HSP90 proteins, named according to the 90 kDa average molecular mass of their members, are highly conserved molecular chaperones that account for 1–2% of all cellular proteins in most cells under non-stress conditions [1]. HSP90 members have key roles in the maturation of signal transduction proteins, like hormone receptors, various kinases, nitric oxide synthase and calcineurin [9,10,11,12,13]. Through these substrates, they regulate diverse cellular processes. HSP90 inhibition provides a recently developed, important pharmacological platform for anticancer therapy [15]
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