Biology subjects

arora, s.

Publications and source records attributed to arora, s..

3 recordsLinked to original sources

bioRxiv2025

Electrostatics Govern Protein Orientation on Citrate-Capped Gold Nanoparticles

Conjugation of proteins with gold nanoparticles (GNPs) is crucial in developing nanoparticle-based drugs, which are used in making targeted delivery systems for therapeutic and diagnostic use. This conjugation is often mediated by covalent gold-thiol (Au-S) bonds involving cysteine residues. However, the influence of other interactions, like electrostatics, on protein-GNP interactions remains poorly understood. While the independent roles of cysteine (thiol interactions) and lysine (electrostatics) are studied, how these two distinct mechanisms couple and mutually influence one another remains unknown. It is particularly unclear how the position and the electrostatics around cysteine residues within the protein structure modulate their interaction with GNPs. Hence, to isolate the electrostatic contribution from Au-S interaction, we systematically investigated the role of positively charged lysine in protein interaction with citrate-capped GNPs using protein L, a cysteine-free antibody-binding protein. Protein L has seven lysine residues, positively charged at pH 7.4. Each lysine was individually mutated to cysteine to create single-cysteine variants. The capping strength of these mutants on citrate-capped GNPs was assessed using various biophysical techniques. Surprisingly, not all cysteine mutants formed stable covalent conjugates. The K7C mutant, in particular, showed strong and irreversible GNP capping, not solely due to the introduced cysteine, but also because of nearby positively charged residues that promoted electrostatic attraction to the negatively charged citrate-capped GNP surface. This critical role of electrostatics was further confirmed using lysine acrylation, which effectively capped lysines and prevented their interaction. Our experimental plan was thus able to successfully decouple the contributions of Au-S bonding from lysine-driven electrostatics. These sequential and cooperative studies underscore that electrostatic and covalent factors are not independent but part of an interconnected process, thereby underscoring the need to consider local charge environments in protein engineering for nanoparticle conjugation.

biophysics↗

bioRxiv2020

RRM2B is frequently amplified across multiple tumor types: non-oncogenic addiction and therapeutic opportunities

RRM2B plays a crucial role in DNA replication, repair and oxidative stress. While germline RRM2B mutations have been implicated in mitochondrial disorders, its relevance to cancer has not been established. Here, using TCGA data, we investigated RRM2B alterations in cancer. We found that RRM2B is highly amplified in multiple tumor types, particularly in MYC-amplified tumors, and is associated with increased RRM2B mRNA expression. We also observed that the chromosomal region 8q22.3-8q24, is amplified in multiple tumors, and includes RRM2B, MYC along with several other cancer-associated genes. An analysis of genes within this 8q-amplicon showed that cases that have both RRM2B-amplified along with MYC have a distinct pattern of amplification compared to unaltered cases or cases that have amplifications in RRM2B or MYC only. These other 8q-proteins were shown to interact functionally within the RRM2B network of DNA repair, hypoxia and apoptosis regulating proteins. Notably, RRM2B-amplified tumors are characterized by mutation signatures of defective DNA repair and oxidative stress, and in some cancers also associated with poor clinical outcome. These findings suggest that some cancers may require RRM2B for cellular survival, providing novel therapeutic opportunities in these cancers.

genomics↗

bioRxiv2020

Phosphine: an eco-friendly alternative for management of wheat storage insects

Methyl bromide (MB) fumigant has been phased out in many countries honouring Montreal Protocol. Reports on phosphine fumigant efficacy under different ecological zones in India are scanty. Field fumigation trials were conducted on 5 Metric Tons of wheat stacks per replication of a treatment for testing phosphine efficacy against laboratory cultured and resident population of Tribolium castanium, Sitophilus oryzae, and Rhyzopertha dominica. The trials were organized in triplicate including control at two locations with varying climate locations namely, Pithoragarh and Delhi using conventional 56% tablet (2 and 3 tablet/MT) and 77.5% granular (1.0 and 1.5 g phosphine/m3) formulations of Aluminium phosphide (AlP) for 7 and 10-days exposure periods for each dosage. Phosphine concentration was monitored every 24 hours till end of the exposure periods. Insect mortality of laboratory culture and resident infestation was observed as 100% in both the exposure periods using all dosages of phosphine. No emergence of insects was observed till 60 days after treatment at both the locations, indicating mortality of all available life stages of insects during the exposure periods. Minimum effective phosphine concentration for controlling all life stages of S. oryzae, R. dominica and T castaneum was observed 500-600 ppm for 7-days exposure at 25{degrees}-27{degrees}C and humidity 38-45%, at 1.5 g phosphine/m3. Hence, phosphine can be an effective alternative to methyl bromide fumigant for wheat stored grain insects at different climatic conditions.

ecology↗