Biology subjects

Orlova, M.

Publications and source records attributed to Orlova, M..

4 recordsLinked to original sources

bioRxiv2021

Cellulonodin-2 and Lihuanodin: Lasso Peptides with an Aspartimide Post-Translational Modification

Lasso peptides are a family of ribosomally synthesized and post-translationally modified peptides (RiPPs) defined by their threaded structure. Besides the class-defining isopeptide bond, other post-translational modifications (PTMs) that further tailor lasso peptides have been previously reported. Using genome mining tools, we identified a subset of lasso peptide biosynthetic gene clusters (BGCs) that are colocalized with protein L-isoaspartyl methyltransferase (PIMT) homologs. PIMTs have an important role in protein repair, restoring isoaspartate residues formed from asparagine deamidation to aspartate. Here we report a new function for PIMT enzymes in the post-translational modification of lasso peptides. The PIMTs associated with lasso peptide BGCs first methylate an L-aspartate sidechain found within the ring of the lasso peptide. The methyl ester is then converted into a stable aspartimide moiety, endowing the lasso peptide ring with rigidity relative to its unmodified counterpart. We describe the heterologous expression and structural characterization of two examples of aspartimide-modified lasso peptides from thermophilic Gram-positive bacteria. The lasso peptide cellulonodin-2 is encoded in the genome of actinobacterium Thermobifida cellulosilytica, while lihuanodin is encoded in the genome of firmicute Lihuaxuella thermophila. Additional genome mining revealed PIMT-containing lasso peptide BGCs in 48 organisms. In addition to heterologous expression, we have reconstituted PIMT-mediated aspartimide formation in vitro, showing that lasso peptide-associated PIMTs transfer methyl groups very rapidly as compared to canonical PIMTs. Furthermore, in stark contrast to other characterized lasso peptide PTMs, the methyltransferase functions only on lassoed substrates. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/444711v1_ufig1.gif" ALT="Figure 1"> View larger version (9K): org.highwire.dtl.DTLVardef@158f0d2org.highwire.dtl.DTLVardef@2a6baeorg.highwire.dtl.DTLVardef@103a91dorg.highwire.dtl.DTLVardef@153dd99_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2020

Built to change: dominance strategy changes with life stage in a primitively eusocial bee

Access to reproduction is determined by an individual dominances rank in many species and is achieved through aggression and/or dominance signalling. In eusocial insects one or several dominant females (queens) monopolize reproduction but to what extent queens rely on aggression and signalling remains obscure. Aggression is costly and its efficiency depends on the group size, whereas signalling may reduce the risks and costs of aggression. Both strategies are used to regulate reproduction in social taxa, with aggression being more common in small social groups, compared to signalling in larger societies. Here, we examine the use of aggression and chemical signalling in a social species (Bombus impatiens) where the dominant queen interacts with increasing numbers of workers as she ages. We found that the queens strategy to monopolize reproduction changes with life stage, shifting from overt aggression to chemical signalling as the queen gets older. Particularly, old queens exhibited a higher ratio of short to long cuticular hydrocarbons compared to young queens, an endogenous shift that was attributed to age, as all egg-laying queens were fecund and kept with the same number of workers. Our findings contribute to the understanding of reproductive dominance in the context of an individuals life history.

evolutionary biology↗

bioRxiv2019

A small family business: synergistic and additive effects of the queen and the brood on worker reproduction in a primitively eusocial bee

The mechanisms that maintain reproductive division of labor in social insects are still incompletely understood. Most studies focus on the relationship between adults, overlooking another important stakeholder in the game - the juvenile offspring. Recent studies from various social species show that not only the queen, but also the brood regulates reproductive division of labor between females, but how the two coordinate to maintain reproductive monopoly remained unexplored.\n\nOur study aims at disentangling the roles of the brood and the queen in regulating worker reproduction in primitively eusocial bees. We examined the effects induced by the brood and queen, separately and together, on the behavioral, physiological and brain gene expression of Bombus impatiens workers. We found that young larvae induce a releaser effect in workers, decreasing egg laying and aggressive behaviors, while the queen induces both releaser and primer effects, modifying worker aggressive and egg laying behavior and reproductive physiology. The expression of reproduction- and aggression-related genes was altered in the presence of both queen and brood, but the effect was stronger or the same in the presence of the queen.\n\nWe identified two types of interactions between the queen and the brood in regulating worker reproduction: (1) synergistic interactions regulating worker physiology, where the combined effect of the queen and the brood was greater than each of them separately; (2) additive interactions regulating worker behavior, where the combined effects of the queen and the brood are the gross sum of their separated effects. In these interactions the brood acted in a manner similar to the queen but to a much smaller extent and improved the quality of the effect induced by the queen. Our results suggest that the queen and the brood of primitively eusocial bees coordinate synergistically, additively, and sometimes even redundantly to regulate worker behavior and reproduction, and the interaction between them exists in multiple regulatory levels.

animal behavior and cognition↗

bioRxiv2019

Pleiotropic effects for Parkin and LRRK2 in leprosy type-1 reactions and Parkinson’s disease

Type-1 reactions (T1Rs) are pathological inflammatory episodes and main contributors to nerve damage in leprosy. Here, we evaluate the gene-wise enrichment of rare protein altering variants in seven genes where common variants were previously associated with T1R. We selected 474 Vietnamese leprosy-patients of which 237 were T1R-affected and 237 were T1R-free matched controls. Gene-wise enrichment of nonsynonymous variants was tested with both kernel based (SKAT) and burden methods. Of the seven genes tested two showed statistical evidence of association with T1R. For the LRRK2 gene an enrichment of nonsynonymous variants was observed in T1R-free controls (p O_SCPCAPSKAT-OC_SCPCAP= 1.6x10-4). This gene-wise association was driven almost entirely by the gain of function variant R1628P (p = 0.004; OR = 0.29). The second gene-wise association was found for the Parkin coding gene PRKN (formerly PARK2) where seven rare variants were enriched in T1R-affected cases (p O_SCPCAPSKAT-OC_SCPCAP = 7.4x10-5). Mutations in both PRKN and LRRK2 are known causes of Parkinsons Disease (PD). Hence, we evaluated to what extent such rare amino acid changes observed in T1R are shared with PD. We observed that nonsynonymous T1R-risk mutations in Parkin were enriched for amino acid mutations implicated in PD (p = 1.5x10-4). Hence, neuro-inflammation in PD and peripheral nerve damage due to inflammation in T1R share overlapping mechanisms of pathogenicity.

genetics↗