Proline-Specific Fungal Peptidases: Genomic Analysis and Identification of Secreted DPP4 in Alkaliphilic and Alkalitolerant Fungi

Proline-specific peptidases (PSP) play a crucial role in the processing of fungal toxins, pheromones, and intracellular signaling. They are of particular interest to biotechnology, as they are able to hydrolyze proline-rich oligopeptides that give a bitter taste to food and can also cause an autoimmune celiac disease. We performed in silico analysis of PSP homologs in the genomes of 42 species of higher fungi which showed the presence of PSP homologs characteristic of various kingdoms of living organisms and belonging to different families of peptidases, including homologs of dipeptidyl peptidase 4 (DPP4) and prolyl aminopeptidase 1 found in almost all the studied fungal species. Homologs of proliniminopeptidases from the S33 family absent in humans were also found. Several studied homologs are characteristic of certain taxonomic groups of fungi. Phylogenetic analysis suggests a duplication of ancestral DPP4 into transmembrane and secreted versions, which predate the split of ascomycete and basidiomycete lineages. Comparative biochemical analysis of DPP4 in alkaliphilic and alkali-tolerant strains of fungi showed that, notwithstanding some individual features of these enzymes, in both cases, the studied DPP4 are active and stable under alkaline conditions and at high salt concentrations, which makes them viable candidates for biotechnology and bioengineering.

Molecular adaptation to calsequestrin 2 (CASQ2) point mutations leading to catecholaminergic polymorphic ventricular tachycardia (CPVT): comparative analysis of R33Q and D307H mutants

Homozygous calsequestrin 2 (CASQ2) point mutations leads to catecholaminergic polymorphic ventricular tachycardia: a common pathogenetic feature appears to be the drastic reduction of mutant CASQ2 in spite of normal transcription. Comparative biochemical analysis of R33Q and D307H knock in mutant mice identifies different pathogenetic mechanisms for CASQ2 degradation and different molecular adaptive mechanisms. In particular, each CASQ2 point mutation evokes specific adaptive cellular and molecular processes in each of the four adaptive pathways investigated. Thus, similar clinical phenotypes and identical cellular mechanism for cardiac arrhythmia might imply different molecular adaptive mechanisms.

Yeast mitochondrial HMG proteins: DNA-binding properties of the most evolutionarily divergent component of mitochondrial nucleoids

Comparative biochemical analysis of mtHMG proteins from distantly related yeast species revealed that they exhibit a preference for recombination/replication intermediates. We discuss how these biochemical characteristics relate to the role of mtHMG proteins in mtDNA compaction and evolution.