Initiation is a critical step in translation, during which the ribosome lands on the start codon and sets the correct reading frame for mRNA decoding. The rate and efficiency of translation are largely determined by initiation, which is therefore the preferred target of translation regulation mechanisms. Initiation has incurred an extensive evolutionary divergence among the primary domains of cell descent. The Archaea, albeit prokaryotes, have an initiation mechanism and apparatus more complex than those of the Bacteria; the molecular details of archaeal initiation are just beginning to be unravelled. The most notable aspects of archaeal initiation are the presence of two, perhaps three, distinct mechanisms for mRNA-ribosome interaction and the presence of a relatively large set of IFs (initiation factors), several of which are shared exclusively with the Eukarya. Among these, the protein termed a/eIF2 (archaeal/eukaryotic IF2) and aIF6 (archaeal IF6) are of special interest, since they appear to play key regulatory roles in the Eukarya. Studies of the function of these factors in Archaea have uncovered new features that will help to elucidate their conserved and domain-specific functions.
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http://dx.doi.org/10.1042/BST0390089 | DOI Listing |
Structure
January 2025
Department of Chemistry, Britannia House, 7 Trinity Street, King's College London, London, SE1 1DB, UK; School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK. Electronic address:
Tripartite resistance nodulation and cell division multidrug efflux pumps span the periplasm and are major drivers of multidrug resistance among gram-negative bacteria. Cations, such as Mg, become concentrated within the periplasm and, in contrast to the cytoplasm, its pH is sensitive to conditions outside the cell. Here, we reveal an interplay between Mg and pH in modulating the structural dynamics of the periplasmic adapter protein, AcrA, and its function within the prototypical AcrAB-TolC multidrug pump from Escherichia coli.
View Article and Find Full Text PDFJ Biomol Struct Dyn
December 2024
Laboratory of Molecular Modeling and Anticancer Drug Development. Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
In about 85% of cancer malignancies, replicative immortality caused by increased telomerase activity makes it an attractive target for developing anticancer therapeutics. However, the lack of approved small-molecule inhibitors rooted in the structural ambiguity of telomerase has impeded drug development for decades. In this study, we have exploited the FVYL pocket in the thumb domain, which plays a key role in the enzyme's processivity.
View Article and Find Full Text PDFCell Commun Signal
December 2024
International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland.
The PD-1/PDL-1 immune checkpoint inhibitors revolutionized cancer treatment, yet osteosarcoma remains a therapeutic challenge. In some types of cancer, PD-1 receptor is not solely expressed by immune cells but also by cancer cells, acting either as a tumor suppressor or promoter. While well-characterized in immune cells, little is known about the role and interactome of the PD-1 pathway in cancer.
View Article and Find Full Text PDFAm J Ind Med
February 2025
Department of Family, Population, and Preventive Medicine, Program in Public Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, USA.
Background: The emergency personnel who responded to the World Trade Center (WTC) attacks endured severe occupational exposures, yet the prevalence of cognitive impairment remains unknown among WTC-exposed-FDNY-responders. The present study screened for mild and severe cognitive impairment in WTC-exposed FDNY responders using objective tests, compared prevalence rates to a cohort of non-FDNY WTC-exposed responders, and descriptively to meta-analytic estimates of MCI from global, community, and clinical populations.
Methods: A sample of WTC-exposed-FDNY responders (n = 343) was recruited to complete an extensive battery of cognitive, psychological, and physical tests.
J Am Soc Mass Spectrom
December 2024
Analytical Chemistry, Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707, United States.
Cysteine residues are crucial for the formation of conserved disulfide bonds in therapeutic monoclonal antibodies (mAbs), which are essential for their folding and structural stability. The presence of free thiols in mAbs can indicate incomplete disulfide bond formation, potentially impacting the molecule's conformational stability. Free thiol quantitation has been achieved using labeling-based strategies such as maleimide and haloalkyl derivatives at both intact and peptide levels.
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