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http://dx.doi.org/10.1038/s41421-022-00489-w | DOI Listing |
ACS Med Chem Lett
January 2025
Bristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, California 92121, United States.
In recent years, targeted protein degradation (TPD) has emerged as a powerful therapeutic modality utilizing both heterobifunctional ligand-directed degraders (LDDs) and molecular glues (e.g., CELMoDs) to recruit E3 ligases for inducing polyubiquitination and subsequent proteasomal degradation of target proteins.
View Article and Find Full Text PDFNat Commun
January 2025
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Transmembrane AMPA receptor regulatory proteins (TARPs) are claudin-like proteins that tightly regulate AMPA receptors (AMPARs) and are fundamental for excitatory neurotransmission. With cryo-electron microscopy (cryo-EM) we reconstruct the 36 kDa TARP subunit γ2 to 2.3 Å, which points to structural diversity among TARPs.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.
Conjugation plays a major role in dissemination of antimicrobial resistance genes. Following transfer of IncF-like plasmids, recipients become refractory to a second wave of conjugation with the same plasmid via entry (TraS) and surface (TraT) exclusion mechanisms. Here, we show that TraT from the pKpQIL and F plasmids (TraT and TraT) exhibits plasmid surface exclusion specificity.
View Article and Find Full Text PDFAutophagy
January 2025
Life Sciences Institute, Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada.
The multi-step macroautophagy/autophagy process ends with the cargo-laden autophagosome fusing with the lysosome to deliver the materials to be degraded. The metazoan-specific autophagy factor EPG5 plays a crucial role in this step by enforcing fusion specificity and preventing mistargeting. How EPG5 exerts its critical function and how its deficiency leads to diverse phenotypes of the rare multi-system disorder Vici syndrome are not fully understood.
View Article and Find Full Text PDFStructure
January 2025
Małopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland. Electronic address:
Deoxyhypusination is the first rate-limiting step of the unique post-translational modification-hypusination-that is catalyzed by deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). This modification is essential for the activation of translation factor 5A in eukaryotes (eIF5A) and Archaea (aIF5A). This perspective focuses on the structural biology of deoxyhypusination complexes in eukaryotic and archaeal organisms.
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