The human T1R2-T1R3 sweet taste receptor (STR) plays an important role in recognizing various low-molecular-weight sweet-tasting sugars and proteins, resulting in the release of intracellular heterotrimeric G protein ...
The human T1R2-T1R3 sweet taste receptor (STR) plays an important role in recognizing various low-molecular-weight sweet-tasting sugars and proteins, resulting in the release of intracellular heterotrimeric G protein that in turn leads to the sweet taste perception. Xylitol and sorbitol, which are naturally occurring sugar alcohols (polyols) found in many fruits and vegetables, exhibit the potential caries-reducing effect and are widely used for diabetic patients as low-calorie sweeteners. In the present study, computational tools were applied to investigate the structural details of binary complexes formed between these two polyols and the T1R2-T1R3 heterodimeric STR. Principal component analysis revealed that the Venus flytrap domain (VFD) of T1R2 monomer was adapted by the induced-fit mechanism to accommodate the focused polyols, in which α-helical residues 233–268 moved significantly closer to stabilize ligands. This finding likely suggested that these structural transformations might be the important mechanisms underlying polyols-STR recognitions. The calculated free energies also supported the VFD of T1R2 monomer as the preferential binding site for such polyols, rather than T1R3 region, in accord with the lower number of accessible water molecules in the T1R2 pocket. The E302 amino acid residue in T1R2 was found to be the important recognition residue for polyols binding through a strongly formed hydrogen bond. Additionally, the binding affinity of xylitol toward the T1R2 monomer was significantly higher than that of sorbitol, making it a sweeter tasting molecule. [ABSTRACT FROM AUTHOR]
The emergence of SARS-CoV in 2002 and SARS-CoV-2 in 2019 led to increased sampling of sarbecoviruses circulating in horseshoe bats. Employing phylogenetic inference while accounting for recombination of bat sarbecovir...
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Methods that link genetic variation to steady-state gene expression levels, such as expression quantitative trait loci (eQTLs), are widely used to functionally annotate trait-associated variants, but they are limited ...
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Radiotherapy is a pillar of breast cancer treatment;however, it remains unclear how radiotherapy modulates the tumor microenvironment. We investigated this question in a cohort of 20 patients with estrogen-receptor po...
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Dense packing of hydrophobic residues in the cores of globular proteins determines their stability. Recently, we have shown that protein cores possess packing fraction ϕ≈0.56, which is the same as dense, random packi...
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Dense packing of hydrophobic residues in the cores of globular proteins determines their stability. Recently, we have shown that protein cores possess packing fraction ϕ≈0.56, which is the same as dense, random packing of amino-acid-shaped particles. In this article, we compare the structural properties of protein cores and jammed packings of amino-acid-shaped particles in much greater depth by measuring their local and connected void regions. We find that the distributions of surface Voronoi cell volumes and local porosities obey similar statistics in both systems. We also measure the probability that accessible, connected void regions percolate as a function of the size of a spherical probe particle and show that both systems possess the same critical probe size. We measure the critical exponent τ that characterizes the size distribution of connected void clusters at the onset of percolation. We find that the cluster size statistics are similar for void percolation in packings of amino-acid-shaped particles and randomly placed spheres, but different from that for void percolation in jammed sphere packings. We propose that the connected void regions are a defining structural feature of proteins and can be used to differentiate experimentally observed proteins from decoy structures that are generated using computational protein design software. This work emphasizes that jammed packings of amino-acid-shaped particles can serve as structural and mechanical analogs of protein cores, and could therefore be useful in modeling the response of protein cores to cavity-expanding and -reducing mutations.
The iterative bleaching extends multiplexity (IBEX) Knowledge-Base is a central portal for researchers adopting IBEX and related 2D and 3D immunofluorescence imaging methods. The design of the Knowledge-Base is modele...
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