The antimicrobial membrane-interacting polypeptide nisin is a prominent member of the lantibiotic family, the members of which contain thioether-bridged residues called lanthionines. To gain insight into the complex biosynthesis and the structure/function relationship of lantibiotics, the final intermediate in the biosynthesis of nisin A was studied by nuclear magnetic resonance spectroscopy. In aqueous solution the leader peptide part of this precursor adopts predominantly a random coil structure, as does the synthetic leader peptide itself. The spatial structure of the fully modified nisin part of the precursor is similar to that of nisin in water. The leader peptide part does not interact with the nisin part of the precursor molecule. Thus, these two parts of the precursor do not influence each other's conformation significantly. The conformation of the precursor was also studied while complexed to micelles of dodecylphosphocholine, mimicking the primary target of the antimicrobial activity of nisin, i.e. the cytoplasmic membrane. The location of the molecule relative to the micelles was investigated by using micelle-inserted spin-labeled 5-doxylstearic acid. It was observed that the N-terminal half of the nisin part of the precursor interacts in a different way with micelles than does the corresponding part of mature nisin, whereas no significant differences were found for the C-terminal half of the nisin part. In this model system the leader peptide is in contact with the micelles. It is concluded that the strongly reduced in vivo activity of the precursor molecule relative to that of nisin is not caused by a difference in the spatial structure of nisin and of the corresponding part of precursor nisin in water or by a shielding of the membrane interaction surface of the nisin part of the precursor by the leader peptide. Probably a different interaction of the N-terminal part of the nisin region with membranes contributes to the low activity by preventing productive insertion. The residues of the leader peptide part just next to the nisin part are likely to contribute most to the low activity of the precursor.
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Sci Rep
January 2025
Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131, Ancona, Italy.
The Low Density Lipoprotein receptors (LDLRs) gene family includes 15 receptors: very low-density lipoprotein receptor (VLDLR), LDLR, Sorting-related receptor with A-type repeats (SORLA), and 12 LDL receptor-related proteins (LRPs): LRP1, LRP1B, LRP2, LRP3, LRP4, LRP5, LRP6, LRP8, LRP10, LRP11, LRP12, LRP13. Most of these are involved in the transduction of key signals during embryonic development and in the regulation of cholesterol homeostasis. In oviparous animals, the VLDL receptor is also known as VTGR since it facilitates the uptake of vitellogenin in ovary.
View Article and Find Full Text PDFInt J Immunogenet
January 2025
Department of Clinical Haematology and Medical Oncology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
High degree of variability in human leukocyte antigens (HLAs) system restricts availability of histocompatible HLA-matched-related donors, thus increasing reliance on worldwide bone marrow registries network. Nevertheless, due to limited coverage/accessibility/affordability of some ethnicities in these registries, haploidentical haematopoietic stem cell transplantation (HSCT) emerged as an alternative option, though with allorecognition-mediated graft versus host disease (GvHD) (>40% cases). A dimorphism [-21 methionine (M) or threonine (T)] in HLA-B leader peptide (exon 1) which differentially influences its HLA-E binding, plausibly regulates natural killer cell functionality, affecting GvHD vulnerability and clinically in practice for donor selection.
View Article and Find Full Text PDFViruses
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School of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
Bombyx mori bidensovirus (BmBDV), a significant pathogen in the sericulture industry, holds a unique taxonomic position due to its distinct segmented single-stranded DNA (ssDNA) genome and the presence of a self-encoding DNA polymerase. However, the functions of viral non-structural proteins, such as NS2, remain unknown. This protein is hypothesized to play a role in viral replication and pathogenesis.
View Article and Find Full Text PDFAm J Reprod Immunol
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GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
Problem: Natural killer (NK) cells undergo education for full functionality via interactions between killer immunoglobulin-like receptors (KIRs) or NKG2A and human leukocyte antigen (HLA) ligands. Presumably, education is important during early pregnancy as insufficient education has been associated with impaired vascular remodeling and restricted fetal growth in mice. NK cell education is influenced by receptor co-expression patterns, human cytomegalovirus (CMV), the HLA-E107 dimorphism, and HLA-B leader peptide variants.
View Article and Find Full Text PDFPLoS Genet
January 2025
Biomedical Science Graduate Program, University of California San Diego, San Diego, California, United States of America.
Proteins with nuclear localization sequences (NLSs) are directed into the cell nucleus through interactions between the NLS and importin proteins. NLSs are generally short motifs rich in basic amino acids; however, identifying NLSs can be challenging due to the lack of a universally conserved sequence. In this study, we characterized the sequence specificity of an essential and conserved NLS in Mcm3, a subunit of the replicative DNA helicase.
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