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Glycosylation of serine/threonine-rich intrinsically disordered regions of membrane-associated proteins in streptococci
2025 / Nature CommunicationsProteins harboring intrinsically disordered regions (IDRs) lacking stable secondary or tertiary structures are abundant across the three domains of life. These regions have not been systematically studied in prokaryotes. Here, our genome-wide analysis identifies extracytoplasmic serine/threonine-rich IDRs in several biologically important membrane-associated prot...
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Deciphering the effects of bixin on pulmonary alveolar adenocarcinoma migration and proliferation via targeting BAX/BCL-2 and Cyclin D1
2025 / Scientific ReportsThere is a tremendous upsurge in lung cancer incidences due to changing lifestyles and other environmental risk factors. Unfortunately, the use of clinical therapeutics is causing serious side effects and drug-resistant tumors. Taking account of the severity of lung cancer malignancy and the pressing need for natural therapeutics, we investigated the anticancer p...
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Photoactuating artificial muscle from supramolecular assembly of an overcrowded alkene-derived molecular switch
2025 / Nature CommunicationsThe amplification of molecular motion along length scales for macroscopic muscle-like functions, based on supramolecular polymers, provides attractive opportunities ranging from soft actuators to responsive biomedical materials. Taking the challenge to reveal dynamic assembly parameters governing muscle functions, we present the design of a photoswitch amphiphile...
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Transformation-associated recombination and heterologous expression of noncanonical depsipeptide nonribosomal peptide synthetase derived from marine Streptomyces
2025 / Marine Life Science & TechnologyAnalysis of the secondary metabolite biosynthesis gene cluster (BGC) from marine Streptomyces sp. SNJ102 revealed the presence of a noncanonical nonribosomal peptide synthetase (NRPS), predicted to produce a depsipeptide compound. The NRPS gene cluster was captured by transformation-associated recombination and heterologously expressed in Streptomyces albus. The ...
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Iron-sensing and redox properties of the hemerythrin-like domains of Arabidopsis BRUTUS and BRUTUS-LIKE2 proteins
2025 / Nature CommunicationsIron uptake in plants is negatively regulated by highly conserved hemerythrin (Hr) E3 ubiquitin ligases exemplified by Arabidopsis thaliana BRUTUS (BTS). Physiological studies suggest these are the elusive plant iron sensors, but biochemical evidence is lacking. Here we demonstrate that the N-terminal domains of BTS and BTS-LIKE2 (BTSL2) respectively bind three a...
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Stability convergence in natural antibodies with ultra-long hypervariable loops
2025 / Communications BiologyAntibodies bind to antigens with hypervariable loops called complementarity-determining regions (CDRs). In contrast to conventional antibodies, a subset of bovine antibodies has an ultra-long CDR (ulCDR) composed of up to 70 residues folded as a stalk and knob. The fundamental principles of how these antibodies maintain their structure and stability remain enigma...
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Filamentous chemokine CCL5 structure and the functional aspects
2025 / Scientific ReportsHuman inflammation-related CC chemokine ligand 5 (hCCL5) has significant self-assembly property under physiological conditions. The mechanism and function of hCCL5 oligomerization remain unclear. Different intermolecular interactions, such as E66-K25 or E66-R44/K45, have been reported to mediate hCCL5 oligomerization. This complexity makes structural determinatio...
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Self-disassembling nanoparticles as oral nanotherapeutics targeting intestinal microenvironment
2025 / Nature CommunicationsInspired by the survival strategies of pyomelanin-producing microbes, we synthesize pyomelanin nanoparticles (PMNPs) from homogentisic acid- γ-lactone via auto-oxidation and investigate their biomedical potential. PMNPs possess distinct physicochemical properties, including reactive oxygen species scavenging and microenvironment-responsive self-disassembly....
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Small glycomimetic antagonists of the cytomegalovirus glycoprotein UL141 prevent binding to TRAIL death receptor
2025 / Journal of Biological ChemistryHuman cytomegalovirus (HCMV) UL141 inhibits immune recognition of virally infected cells by natural killer cells and cytotoxic T cells through modulation of cellular receptors (e.g., TRAIL-R2/-R1, CD155, CD112). Recent findings suggest that UL141 is also a critical component of the HCMV virion, further emphasizing its significance. In this study, we aimed to deve...
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Mechanistic insights into the structure-based design of a CspZ-targeting Lyme disease vaccine
2025 / Nature CommunicationsBorrelia burgdorferi (Bb) causes Lyme disease (LD), one of the most common vector-borne diseases in the Northern Hemisphere. Here, we solve the crystal structure of a mutated Bb vaccine antigen, CspZ-YA that lacks the ability to bind to host complement factor H (FH). We generate point mutants of CspZ-YA and identify CspZ-YAI183Y and CspZ-YAC187S to trigger more r...
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Molecular networking reveals indole diterpenoids from the marine-derived fungus Penicillium sp. N4-3
2025 / Marine Life Science & TechnologyMS/MS-based molecular networking is an effective strategy to rapidly dereplicate known compounds and to guide the discovery process for new and novel natural products. In the present study, the chemical diversity of indole diterpenoids from the marine-derived fungus Penicillium sp. N4-3 was investigated using molecular networking techniques. Guided by this inform...
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Role of charges in a dynamic disordered complex between an IDP and a folded domain
2025 / Nature CommunicationsProtein complexes involving intrinsically disordered proteins (IDPs) cover a continuum from IDPs that fully fold upon binding to IDPs that remain fully disordered in the complex. Here we demonstrate a case of charge-driven interactions of a folded domain with an oppositely charged IDP that remains completely disordered in the complex. Using the negatively charged a...
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Divergent dimerization mechanisms and conserved DNA-binding function in PFam12 proteins of Borrelia burgdorferi
2025 / Scientific ReportsLyme disease, caused by the spirochete Borrelia burgdorferi, is transmitted to mammalian hosts during the feeding process of infected Ixodes ticks. Our previous studies demonstrated that the paralogous gene family 12 (PFam12) consisting of five members (BBK01, BBG01, BBH37, BBJ08, and BB0844) are non-specific DNA-binding proteins. PFam12 proteins share 31–6...
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Design, development, and preclinical evaluation of pirfenidone-loaded nanostructured lipid carriers for pulmonary delivery
2025 / Scientific ReportsPirfenidone is an antifibrotic and anti-inflammatory drug used for the management of idiopathic pulmonary fibrosis. The current oral delivery of PD has multiple drawbacks, including first-pass metabolism and gastrointestinal discomfort. Efforts have been made to create nanostructured lipid carriers (NLCs) using solid lipids, liquid lipids, and surfactants through...
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Synthesis of novel sulphonamide derivatives from tunable quinolines with computational studies
2025 / Scientific ReportsThe synthesis of new quinoline-sulphonamide derivatives was accomplished through a meticulous five-step molecular assembly utilizing Suzuki, acid–amine cross-coupling reactions and N-alkylation. The integrity of each derivative was thoroughly confirmed via comprehensive spectroscopic analyses, including 1H and 13C NMR, DEPT-135, 1H-1H COSY, HSQC NMR and HRM...
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