Biology subjects

Safdari, H.

Publications and source records attributed to Safdari, H..

7 recordsLinked to original sources

bioRxiv2026

The LudP arrest peptide stalls translation by remodeling the ribosomal A-site

Bacterial ribosome arrest peptides couple translation to secretion and membrane homeostasis, providing an intracellular regulatory feedback system. Although several Sec/YidC-associated arrest peptides have been characterized, how evolutionarily diverse peptides converge on equivalent physiological outcomes remains unclear. Here we identify LudP (Lacrimispora upstream of secDF peptide), a previously unrecognized arrest peptide conserved in the genus Lacrimispora and encoded immediately upstream of secDF. In vitro and in vivo assays show that LudP induces robust Gram-positive-specific translation arrest that is released in a Sec signal-dependent manner. Using systematic mutagenesis and deep mutational scanning, we define a compact 15-residue C-terminal arrest element that governs arrest stability and A-site residue selectivity. Cryo-electron microscopy reveals that a LudP nascent-chain -helix in the exit tunnel remodels the peptidyltransferase center, with Asp133-dependent conformational rearrangements of 23S rRNA, notably U2506, sterically and energetically destabilizing productive A-site aminoacyl-tRNA accommodation. These findings support functional convergent evolution of secretion-coupled arrest peptides across bacterial lineages.

molecular biology↗

bioRxiv2025

Blocking IF3N delays bacterial translation initiation

The authors have withdrawn this manuscript because reviewers have suggested significant revisions which required major restructuring of the manuscript. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

biochemistry↗

bioRxiv2022

Structural basis for translation inhibition 1 by the glycosylated antimicrobial peptide Drosocin from Drosophila melanogaster

The proline-rich antimicrobial peptide (PrAMP) drosocin is produced by Drosophila species to combat bacterial infection. Unlike many PrAMPs, drosocin is O-glycosylated at threonine 11, a post-translation modification that enhances its antimicrobial activity. Here we demonstrate that the O-glycosylation influences not only cellular uptake of the peptide, but also interacts with its intracellular target, the ribosome. Cryo-electron microscopy structures of glycosylated drosocin on the ribosome at 2.1-2.8 [A] resolution reveal that the peptide interferes with translation termination by binding within the polypeptide exit tunnel and trapping RF1 on the ribosome, reminiscent of that reported for the PrAMP apidaecin. The glycosylation of drosocin enables multiple interactions with U2609 of the 23S rRNA, leading to conformational changes that break the canonical base-pair with A752. Collectively, our study provides novel molecular insights into the interaction of O-glycosylated drosocin with the ribosome, which provides a structural basis for future development of this class of antimicrobials.

biochemistry↗

bioRxiv2019

The lottery of spermatogenesis

The causes of male infertility are yet to be fully understood. Here, we propose that male infertility can be partly attributed to the insufficiency of cytoplasmically-inherited proteins in sperms. Using a simple stochastic model of spermatogenesis, we show that in a range of parameters, the proportion of viable sperms can be reduced simply due to stochastic transmission of proteins from spermatogonia to spermatids.

developmental biology↗

bioRxiv2019

A hierarchical approach to model decision making: a study in chemotactic behavior of Escherichia coli

Reducing the complex behavior of living entities to its underlying physical and chemical processes is a formidable task in biology. Complex behaviors can be characterized as decision making: the ability to process the incoming information via an intracellular network and act upon this information to choose appropriate strategies. Motility is one such behavior that has been the focus many modeling efforts in the past. Our aim is to reduce the chemotactic behavior in E. coli to its molecular constituents in order to paint a comprehensive and end-to-end picture of this intricate behavior. We utilize a hierarchical approach, consisting of three layers, to achieve this goal: at the first level, chemical reactions involved in chemotaxis are simulated. In the second level, the chemical reactions give rise to the mechanical movement of six independent flagella. At the last layer, the two lower layers are combined to allow a digital bacterium to receive information from its environment and swim through it with verve. Our results are in concert with the experimental studies concerning the motility of E. coli cells. In addition, we show that our detailed model of chemotaxis is reducible to a non-homogeneous Markov process.

systems biology↗

bioRxiv2019

Making ATP fast and slow: do yeasts play a mixed strategy to metabolise glucose?

The ability of some microorganisms to switch from respiration to fermentation in the presence of oxygen-the so-called Crabtree effect-has been a fascinating subject of study at the theoretical and experimental fronts. Game-theoretical approaches have been routinely used to examine and explain the way a microorganism, such as yeast, would switch between the two ATP-producing pathways, i.e., respiration and fermentation. Here we attempt to explain the switch between respiration and fermentation in yeast by constructing a simple metabolic switch. We then utilise an individual-based model, in which each individual is equipped with all the relevant chemical reactions, to see how cells equipped with such metabolic switch would behave in different conditions. We further investigate our proposed metabolic switch using the game-theoretical approach. Based on this model, we postulate that individuals play a mixed game of glucose metabolism in the population. This approach not only sheds some light in the varieties of metabolic regulations that can be utilised by the individual in the population in competition with others for a common resource, it would also allow a better understanding of the causes of the Warburg effect and similar phenomena observed in nature.

systems biology↗

bioRxiv2017

Noise-driven Cell Differentiation and the Emergence of Organization

One of the major transitions in evolution is the step from unicellularity into the brave new world of multicellularity. To understand this feat, one has to fathom two main characteristics of multicellular organisms: differentiation and self-organization. Any explanation concerning this major transition should involve mechanisms that can simultaneously explain the marvellous intricacies manifest in the aforementioned characteristics, and an account of the evolution of such traits. Here we propose a noise-driven differentiation (NDD) model. The reliance on noise, in place of a more mechanistic approach, makes the NDD model a more suitable approach to explain differentiation and self-organization. Furthermore, our model sheds some light on the possible evolutionary origins of these biological innovations. To test the NDD model, we utilize a model of cell aggregation. The behavior of this model of cell aggregation is in concert with the NDD model.

cell biology↗