The mechanical and electrical properties, and information processing capabilities of microtubules are the permanent subject of interest for carrying out experiments in vitro and in silico, as well as for theoretical attempts to elucidate the underlying processes. In this paper, we developed a new model of the mechano-electrical waves elicited in the rows of very flexible C-terminal tails which decorate the outer surface of each microtubule. The fact that C-terminal tails play very diverse roles in many cellular functions, such as recruitment of motor proteins and microtubule-associated proteins, motivated us to consider their collective dynamics as the source of localized waves aimed for communication between microtubule and associated proteins. Our approach is based on the ferroelectric liquid crystal model and it leads to the effective asymmetric double-well potential which brings about the conditions for the appearance of kink-waves conducted by intrinsic electric fields embedded in microtubules. These kinks can serve as the signals for control and regulation of intracellular traffic along microtubules performed by processive motions of motor proteins, primarly from kinesin and dynein families. On the other hand, they can be precursors for initiation of dynamical instability of microtubules by recruiting the proper proteins responsible for the depolymerization process.
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Sci Adv
January 2025
Atelier de Biologie Chimie Informatique Structurale, Centre de Biologie Structurale, Univ Montpellier, CNRS, INSERM, 29 rue de Navacelles, 34090 Montpellier, France.
Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a crucial reducing cofactor for reductive biosynthesis and protection from oxidative stress. To fulfill their heightened anabolic and reductive power demands, cancer cells must boost their NADPH production. Progrowth and mitogenic protein kinases promote the activity of cytosolic NAD kinase (NADK), which produces NADP, a limiting NADPH precursor.
View Article and Find Full Text PDFJ Med Chem
January 2025
Zealand Pharma A/S, Sydmarken 11, 2860 Søborg, Denmark.
Human glucagon-like peptide-2 (hGLP-2) receptor agonists have a benefit for the treatment of short bowel syndrome (SBS) and potentially other intestinal diseases (e.g., IBD).
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Research Center for Analytical Sciences, Tianjin Key Laboratory of Biosensing and Molecular Recognition, State Key Laboratory of Medicinal Chemical, Biology College of Chemistry, Nankai University, Tianjin 300071, China.
PGLa, an antimicrobial peptide (AMP), primarily exerts its antibacterial effects by disrupting bacterial cell membrane integrity. Previous theoretical studies mainly focused on the binding mechanism of PGLa with membranes, while the mechanism of water pore formation induced by PGLa peptides, especially the role of structural flexibility in the process, remains unclear. In this study, using all-atom simulations, we investigated the entire process of membrane deformation caused by the interaction of PGLa with an anionic cell membrane composed of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG).
View Article and Find Full Text PDFDev Reprod
December 2024
Carbon-Neutral Resources Research Center, Institute of Genetic Engineering, Hankyong National University, Anseong 17579, Korea.
Lutropin/choriogonadotropin receptor (LH/CGR) is a member of the G protein-coupled receptor superfamily. LH/CGRs in fish and mammalian species have been reported to contain naturally occurring, constitutively activating, and inactivating mutations in highly conserved regions. The present study was designed to determine the functional aspect of eel LH/CGR signal transduction.
View Article and Find Full Text PDFNat Commun
January 2025
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Ubiquitin-specific protease 18 (USP18) is a multifunctional cysteine protease primarily responsible for deconjugating the interferon-inducible ubiquitin-like modifier ISG15 from protein substrates. Here, we report the design and synthesis of activity-based probes (ABPs) that incorporate unnatural amino acids into the C-terminal tail of ISG15, enabling the selective detection of USP18 activity over other ISG15 cross-reactive deubiquitinases (DUBs) such as USP5 and USP14. Combined with a ubiquitin-based DUB ABP, the USP18 ABP is employed in a chemoproteomics screening platform to identify and assess inhibitors of DUBs including USP18.
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