Development of luminescent segmented heterostructures featuring multiple spatial-responsive blocks is important to achieve miniaturized photonic barcodes toward anti-counterfeit applications. Unfortunately, dynamic manipulation of the spatial color at micro/nanoscale still remains a formidable challenge. Here, a straightforward strategy is proposed to construct spatially varied heterostructures through amplifying the conformation-driven response in flexible lanthanide-metal-organic frameworks (Ln-MOFs), where the thermally induced minor conformational changes in organic donors dramatically modulate the photoluminescence of Ln acceptors. Notably, compositionally and structurally distinct heterostructures (1D and 2D) are further constructed through epitaxial growth of multiple responsive MOF blocks benefiting from the isomorphous Ln-MOF structures. The thermally controlled emissive colors with distinguishable spectra carry the fingerprint information of a specific heterostructure, thus allowing for the effective construction of smart photonic barcodes with spatially responsive characteristics. The results will deepen the understanding of the conformation-driven responsive mechanism and also provide guidance to fabricate complex stimuli-responsive hierarchical microstructures for advanced optical recording and high-security labels.

In this work, binding interactions of artemisinin (ART) and dihydroartemisinin (DHA) with human serum albumin (HSA) and bovine serum albumin (BSA) were investigated thoroughly to illustrate the conformational variation of serum albumin. Experimental results indicated that ART and DHA bound strongly with the site I of serum albumins via hydrogen bond (H-bond) and van der Waals force and subsequently statically quenched the intrinsic fluorescence of serum albumins through concentration-dependent manner. The quenching abilities of two drugs on the intrinsic fluorescence of HSA were much higher than the quenching abilities of two drugs on the intrinsic fluorescence of BSA. Both ART and DHA, especially DHA, caused the conformational variation of serum albumins and reduced the α-helix structure content of serum albumins. DHA with hydrophilic hydroxyl group bound with HSA more strongly, suggesting the important roles of the chemical polarity and the hydrophilicity during the binding interactions of two drugs with serum albumins. These results reveal the molecular understanding of binding interactions between ART derivatives and serum albumins, providing vital information for the future application of ART derivatives in biological and clinical areas.

In this paper, Ti3C2 quantum dots (Ti3C2 QDs) were synthesized by simply treating Ti3C2 MXene powder with acid and base via hydrothermal method. Ti3C2 QDs exhibited superior fluorescence property and were used for the fluorescent imaging of living HeLa cells successfully. In order to evaluate the influence of Ti3C2 QDs on protease with specific biological functions, binding interaction of Ti3C2 QDs with trypsin was studied comprehensively and deeply through spectroscopic strategies and molecular modeling technique. The intrinsic fluorescence of trypsin was spontaneously quenched by Ti3C2 QDs through static quenching mode under van der Waals interaction force, and Ti3C2 QDs bound with the inactive residue domain of trypsin firmly with stoichiometric ratio of 1:1. Ti3C2 QDs induced the microenvironmental variation of the amino acid residues in trypsin, reducing the thermal stability of trypsin significantly. Gel electrophoresis experiments and microscopic imaging experiments demonstrated that Ti3C2 QDs inhibited the enzymatic activity of trypsin on the digestion of human serum albumin and HeLa cells obviously. These results revealed not only the deep interaction mechanism between Ti3C2 QDs and protease but also the influence of Ti3C2 QDs on the enzymatic activity of trypsin, paving the way for the safe biological application of Ti3C2 QDs in the diagnosis and the therapy of protease-related diseases.

Interactions between gluten proteins and water-extractable arabinoxylan (WEAX) during the heating stage are crucial for the organoleptic quality of high-fiber cereal products. To reveal the molecular mechanism of WEAX on gluten characteristic upon heating, the current study comparatively investigated the effects of WEAX with different molecular weights (Mw) on the heat-evoked conformational variation and polymerization behavior of gluten. Results showed that WEAX, especially low Mw WEAX (L-WEAX), facilitated the polymerization ability of α-/γ-gliadins into glutenins, whereas high Mw WEAX (H-WEAX) reduced the polymerizing temperature of glutenin and gliadin. L-WEAX could develop more hydrogen bonds with tyrosine of gluten and stabilize the secondary structure more evidently than H-WEAX upon heating. Compared with disulfide bridge formation, hydrophobic interactions were not the driving force involved in the heat-induced polymerization behavior affected by WEAX. WEAX evoked the reinforced glutenin network and heterogeneous distribution of gliadin, with a more uniform molecular surface developed for gluten.

Direct-acting antivirals (DAAs) targeting the non-structural 5A (NS5A) protein of the hepatitis C virus (HCV) are crucial drugs that have shown exceptional clinical success in patients. However, their mode of action (MoA) remains unclear, and drug-resistant HCV strains are rapidly emerging. It is critical to characterize the behaviour of the NS5A protein in solution, which can facilitate the development of new classes of inhibitors or improve the efficacy of the currently available DAAs. Using biophysical methods, including dynamic light scattering, size exclusion chromatography and chemical cross-linking experiments, we showed that the NS5A domain 1 from genotypes 1b and 1a of the HCV intrinsically self-associated and existed as a heterogeneous mixture in solution. Interestingly, the NS5A domain 1 from genotypes 1b and 1a exhibited different dynamic equilibria of monomers to higher-order structures. Using small-angle X-ray scattering, we studied the structural dynamics of the various states of the NS5A domain 1 in solution. We also tested the effect of daclatasvir (DCV), the most prominent DAA, on self-association of the wild and DCV-resistant mutant (Y93H) NS5A domain 1 proteins, and demonstrated that DCV induced the formation of large and irreversible protein aggregates that eventually precipitated out. This study highlights the conformational variability of the NS5A domain 1 of HCV, which may be an intrinsic structural behaviour of the HCV NS5A domain 1 in solution.

Single-particle electron cryo-microscopy (cryo-EM) is an emerging tool for resolving structures of conformationally heterogeneous particles; however, each structure is derived from an average of many particles with presumed identical conformations. We used a 3.5-Å cryo-EM reconstruction with imposed D7 symmetry to further analyze structural heterogeneity among chemically identical subunits in each GroEL oligomer. Focused classification of the 14 subunits in each oligomer revealed three dominant classes of subunit conformations. Each class resembled a distinct GroEL crystal structure in the Protein Data Bank. The conformational differences stem from the orientations of the apical domain. We mapped each conformation class to its subunit locations within each GroEL oligomer in our dataset. The spatial distributions of each conformation class differed among oligomers, and most oligomers contained 10-12 subunits of the three dominant conformation classes. Adjacent subunits were found to more likely assume the same conformation class, suggesting correlation among subunits in the oligomer. This study demonstrates the utility of cryo-EM in revealing structure dynamics within a single protein oligomer.

Temperature variation caused by climate change, seasonal variation and geographic locations affects the physicochemical compositions of chromophoric dissolved organic matter (CDOM), resulting in difference in the fates of CDOM-related environmental pollutants. Exploration into the thermal induced structural transition of CDOM can help to better understand their environmental impacts, but information on this aspect is still lacking. Through integrating fluorescence excitation-emission matrix coupled parallel factor analysis with synchronous fluorescence two-dimensional correlation spectroscopy, this study provides an in-depth insight into the temperature-dependent conformational transitions of CDOM and their impact on its hydrophobic interaction with persistent organic pollutants (with phenanthrene as an example) in water. The fluorescence components in CDOM change linearly to water temperature with different extents and different temperature regions. The thermal induced transition priority in CDOM is protein-like component → fulvic-like component → humic-like component. Furthermore, the impact of thermal-induced conformational transition of CDOM on its hydrophobic interaction with phenanthrene is observed and explored. The fluorescence-based analytic results reveal that the conjugation degree of the aromatic groups in the fulvic- and humic-like substances, and the unfolding of the secondary structure in the protein-like substances with aromatic structure, contribute to the conformation variation. This integrated approach jointly enhances the characterization of temperature-dependent conformational variation of CDOM, and provides a promising way to elucidate the environmental behaviours of CDOM.

Human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) is a disease pertained to the human immune system. Given its crucial role in viral replication, HIV-1 protease (HIV-1 PR) is a prime therapeutic target in AIDS therapy. In this regard, the dynamic aspects of ligand-enzyme interactions may indicate an important role of conformational variability in HIV-1 PR inhibitor/drug design. In the present contribution, the effect of HIV-1 PR flexibility (within multiple crystallographic structures of HIV-1 PR) on binding to the Amprenavir was elucidated via an ensemble docking approach. Molecular docking studies were performed via advanced AutoDock4.2 software. Ensemble docking of Amprenavir into the active site of various conformations of HIV-1 PR predicted different interaction modes/energies. Analysis of binding factors in terms of docking false negatives/positives revealed a determinant role of enzyme conformational variation in prediction of optimum induced fit (PDB ID: 1HPV). The outcomes of this study demonstrated that conformation of receptor may significantly affect the accuracy of docking/binding results in structure-based rational design of anti HIV-1 PR agents. Furthermore; some strategies to re-score the docking results in HIV-1 PR targeted docking studies were proposed.

C. elegans MnSOD-3 has been implicated in the longevity pathway and its mechanism of catalysis is relevant to the aging process and carcinogenesis. The structures of MnSOD-3 provide unique crystallographic evidence of a dynamic region of the tetrameric interface (residues 41-54). We have determined the structure of the MnSOD-3-azide complex to 1.77-Å resolution. Analysis of this complex shows that the substrate analog, azide, binds end-on to the manganese center as a sixth ligand and that it ligates directly to a third and new solvent molecule also positioned within interacting distance to the His30 and Tyr34 residues of the substrate access funnel. This is the first structure of a eukaryotic MnSOD-azide complex that demonstrates the extended, uninterrupted hydrogen-bonded network that forms a proton relay incorporating three outer sphere solvent molecules, the substrate analog, the gateway residues, Gln142, and the solvent ligand. This configuration supports the formation and release of the hydrogen peroxide product in agreement with the 5-6-5 catalytic mechanism for MnSOD. The high product dissociation constant k4 of MnSOD-3 reflects low product inhibition making this enzyme efficient even at high levels of superoxide.