In G protein-coupled receptors (GPCRs), the interaction between the cytosolic ends of transmembrane helix 3 (TM3) and TM6 was shown to play an important role in the transition from inactive to active states. According to the currently prevailing model, constructed for rhodopsin and structurally related receptors, the arginine of the conserved "DRY" motif located at the cytosolic end of TM3 (R3.50) would interact with acidic residues in TM3 (D/E3.49) and TM6 (D/E6.30) at the resting state and shift out of this polar pocket upon agonist stimulation. However, 30% of GPCRs, including all chemokine receptors, contain a positively charged residue at position 6.30 which does not support an interaction with R3.50. We have investigated the role of R6.30 in this receptor family by using CCR5 as a model. R6.30D and R6.30E substitutions, which allow an ionic interaction with R3.50, resulted in an almost silent receptor devoid of constitutive activity and strongly impaired in its ability to bind chemokines but still able to internalize. R6.30A and R6.30Q substitutions, allowing weaker interactions with R3.50, preserved chemokine binding but reduced the constitutive activity and the functional response to chemokines. These results indicate that the constitutive and ligand-promoted activity of CCR5 can be modified by modulating the interaction between the DRY motif in TM3 and residues in TM6 suggesting that the overall structure and activation mechanism are well conserved in GPCRs. However, the molecular interactions locking the inactive state must be different in receptors devoid of D/E6.30.
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http://dx.doi.org/10.1016/j.cellsig.2007.01.022 | DOI Listing |
Gut Microbes
December 2025
Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University, Chengdu, China.
Necrotizing Enterocolitis (NEC) is a severe, life-threatening inflammatory condition of the gastrointestinal tract, especially affecting preterm infants. This review consolidates evidence from various biomedical disciplines to elucidate the complex pathogenesis of NEC, integrating insights from clinical, microbial, and molecular perspectives. It emphasizes the modulation of NEC-associated inflammatory pathways by probiotics and novel biologics, highlighting their therapeutic potential.
View Article and Find Full Text PDFPhotochem Photobiol Sci
January 2025
Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, 400094, India.
The efficacy of photodynamic treatment (PDT) against deep-seated tumor is hindered by low penetration depth of light as well as hypoxic conditions which prevails in tumor. To overcome this limitation, Near-infrared (NIR) absorbing photosensitizers have been investigated actively. In the present study we evaluated the PDT efficacy of an NIR absorbing chlorophyll derivative 'Cycloimide Purpurin-18 (CIPp-18)' in Human Breast carcinoma (MCF-7) and cervical adenocarcinoma (Hela) cells under normoxic and hypoxic conditions.
View Article and Find Full Text PDFBiomol NMR Assign
January 2025
High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.
PhoCl is a photocleavable protein engineered from a green-to-red photoconvertible fluorescent protein by circular permutation, and has been used in various optogenetic applications including precise control of protein localization and activity in cells. Upon violet light illumination, PhoCl undergoes a β-elimination reaction to be cleaved at the chromophore, resulting in spontaneous dissociation into a large empty barrel and a small C-terminal peptide. However, the structural determinants and the mechanism of the PhoCl photocleavage remain elusive, hindering the further development of more robust photocleavable optogenetic tools.
View Article and Find Full Text PDFBiomol NMR Assign
January 2025
Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, 06030, USA.
The nutrient germinant receptors (GRs) in spores of Bacillus species consist of a cluster of three proteins- designated A, B, and C subunits- that play a critical role in initiating the germination of dormant spores in response to specific nutrient molecules. The Bacillus cereus GerI GR is essential for inosine-induced germination; however, the roles of the individual subunits and the mechanism by which germinant binding activates GR function remain unclear. In this study, we report the backbone chemical shift assignments of the N-terminal domain (NTD) of the A subunit of GerI (GerIA).
View Article and Find Full Text PDFGeroscience
January 2025
National Institute On Aging, Bethesda, MD, USA.
Photobiomodulation (PBM) therapy, a non-thermal light therapy using nonionizing light sources, has shown therapeutic potential across diverse biological processes, including aging and age-associated diseases. In 2023, scientists from the National Institute on Aging (NIA) Intramural and Extramural programs convened a workshop on the topic of PBM to discuss various proposed mechanisms of PBM action, including the stimulation of mitochondrial cytochrome C oxidase, modulation of cell membrane transporters and receptors, and the activation of transforming growth factor-β1. They also reviewed potential therapeutic applications of PBM across a range of conditions, including cardiovascular disease, retinal disease, Parkinson's disease, and cognitive impairment.
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