Biology subjects

KAUR, A.

Publications and source records attributed to KAUR, A..

5 recordsLinked to original sources

bioRxiv2025

Effects of Calreticulin Mutations on HLA Class I Expression in Myeloproliferative Neoplasms

Calreticulin (CRT) is important for human leukocyte antigen (HLA) class I assembly. Somatic mutations of the CRT gene (CALR) in hematopoietic lineage cells cause myeloproliferative neoplasms (MPNs). Typically, MPN patient cells have one copy each of the wild-type and mutant CALR allele. We find that heterozygous knock-in of a MPN CALR mutation into human cell lines maintains or slightly induces surface expression of HLA class I allotypes. However, full deficiency of wild-type CRT variably reduces the surface expression of HLA class I allotypes, and MPN CRT mutants fail to restore expression for all tested allotypes. Consistent with the largely heterozygous nature of CALR mutations in MPN, surface HLA class I expression in platelets and monocytes from MPN patients with CALR mutations generally falls within the normal range, with higher average expression measured in monocytes from patients treated with interferon alpha compared with other treatments. Overall, the studies indicate that loss of HLA class I expression in cells deficient in wild-type CRT (the CRT dependency) is allele-dependent and correlates with known effects of the assembly factor tapasin. Furthermore, heterozygous knock-in of a MPN-linked CALR mutation has no effect on some allotypes and slightly induces HLA class I expression for CRT-dependent allotypes.

immunology↗

bioRxiv2023

Conformational Dynamics and metal-ion interactions in human small Ubiquitin-like modifier (SUMO2)

SUMO (Small Ubiquitin-like Modifiers) proteins are involved in a crucial post-translational modification commonly termed as SUMOylation. Currently little is known about localisation and accumulation of SUMO2 conjugates in response to proteasome inhibitors. In this work, we have investigated a strong binding of Cu2+ ions in the C-terminal region of SUMO2 resulting in its aggregation and seems to interefere in its non-covalent interaction with a V/I-X-V/I-V/I based SIM. In Ubiquitin-proteasome system, SUMO2 controls many targets in regulation of all aspects of metabolism. The conformational flexibility of SUMO2 could play a crucial role, therefore we have also characterized native-state flexibility of human SUMO2. We show that compared to SUMO1, several amino acids in SUMO2 around 1-helix region access energetically similar near-native conformations. This could play a fundamental role in its non-covalent interactions with SUMO interaction motifs (SIMs).

biochemistry↗

bioRxiv2023

Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing

Activation of CD8+ T cells against pathogens and cancers involves the recognition of antigenic peptides bound to human leukocyte antigen (HLA) class-I proteins. Peptide binding to HLA class I proteins is coordinated by a multi-protein complex called the peptide loading complex (PLC). Tapasin, a key PLC component, facilitates the binding and optimization of HLA class I peptides. However, different HLA class I allotypes have variable requirements for tapasin for their assembly and surface expression. HLA-B*44:02 and HLA-B*44:05, which differ only at residue 116 of their heavy chain sequences, fall at opposite ends of the tapasin-dependency spectrum. HLA-B*44:02 (D116) is highly tapasin-dependent, whereas HLA-B*44:05 (Y116) is highly tapasinindependent. Mass spectrometric comparisons of HLA-B*4405 and HLA-B*44:02 peptidomes were undertaken to better understand the influences of tapasin upon HLA-B44 peptidome compositions. Analyses of the HLA-B*44:05 peptidomes in the presence and absence of tapasin reveal that peptides with the C-terminal tryptophan residues and those with higher predicted binding affinities are selected in the presence of tapasin. Additionally, when tapasin is present, C-terminal tryptophans are also more highly represented among peptides unique to B*44:02 and those shared between B*44:02 and B*44:05, compared with peptides unique to B*44:05. Overall, our findings demonstrate that tapasin influences the C-terminal composition of HLA class I-bound peptides and favors the binding of higher affinity peptides. For the HLA-B44 family, the presence of tapasin or high tapasin-dependence of an allotype results in better binding of peptides with C-terminal tryptophans, consistent with a role for tapasin in stabilizing an open conformation to accommodate bulky C-terminal residues.

immunology↗

bioRxiv2020

Cloning and characterization of Osmotin (OsmSt) alleles from potato cultivar Kufri Chipsona 1

The present study was focussed to clone and sequence characterise alleles of osmotin from cDNA of Solanum tuberosum L. cultivar Kufri Chipsona 1. The genes vary in sizes as well as were found to have eleven point mutations throughout the coding sequence. One deletion of 7 bp was also found in smaller form of the gene having molecular weight of 19.91 KDa. Osmotin gene is known to impart resistance/tolerance to various fungal diseases in addition to its role as an osmoprotectant, thus, cloned osmotin alleles from important processing grade potato cultivar could become potential candidates for molecular breeding of potato.

plant biology↗

bioRxiv2020

The Effect of Gelling agent, medium pH and silver nitrate on adventitious shoot regeneration in Solanum tuberosum

Vegetative propagation of potato makes the crop vulnerable to many seed borne diseases. The importance of the crop in attainment of food security makes it an important candidate for in vitro propagation and genetic manipulations. To undertake crop improvement programmes, development of an efficient regeneration protocol is a pre-requisite. Therefore, the present report was focussed to study various factors affecting shoot organogenesis in potato cultivar Kufri Chipsona 1. The incorporation of silver nitrate (10 {micro}M) to the regeneration medium (MS medium supplemented with BA and GA3) was found to induce shoot organogenesis in 32.11% of leaf and 59.99% of internodal explants. An increase in mean number of shoots regenerated per leaf (5.31) and internodal (8.67) explant was also observed upon addition of silver nitrate to the medium. Similarly, solidification of medium with clarigel and its adjustment to pH 5.8 was found optimum for increasing shoot organogenesis frequency in potato. Among the two types of explants tested, a better response was observed from internodes in comparison with leaf explants. The regenerated shoots were tested for clonal fidelity using PCR based molecular markers [Random Amplified Polymorphic DNA (RAPD) and Inter-Simple Sequence Repeats (ISSR)] and were found true to type.

plant biology↗