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The contraction-relaxation cycle of muscle cells translates into large movements of several filament systems in sarcomeres, requiring special molecular mechanisms to maintain their structural integrity. Recent structural and functional data from three filaments harboring extensive arrays of immunoglobulin-like domains - titin, filamin and myomesin--have, for the first time, unraveled a common function of their terminal domains: assembly and anchoring of the respective filaments. In each case, the protein-protein interactions are mediated by antiparallel dimerization modules via intermolecular beta-sheets. These observations on terminal filament assembly indicate an attractive model for several other filament proteins that require structural characterization.
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http://dx.doi.org/10.1016/j.tibs.2008.09.009 | DOI Listing |
Anal Chem
September 2025
Jiaxing Key Laboratory of Molecular Recognition and Sensing, College of Biological and Chemical Engineering, Jiaxing University, Jiaxing 314001, China.
Despite the promise of electrochemical biosensors in amplified nucleic acid diagnostics, existing high-sensitivity platforms often rely on a multilayer surface assembly and cascade amplification confined to the electrode interface. These stepwise strategies suffer from inefficient enzyme activity, poor mass transport, and inconsistent probe orientation, which compromise the amplification efficiency, reproducibility, and practical applicability. To address these limitations, we report a programmable dual-phase electrochemical biosensing system that decouples amplification from signal transduction.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States.
Among the different types of HIV-1 maturation inhibitors, those that stabilize the junction between the capsid protein C-terminal domain (CA) and the spacer peptide 1 (SP1) within the immature Gag lattice are promising candidates for antiretroviral therapies. Here, we report the atomic-resolution structure of CA-SP1 assemblies with the small-molecule maturation inhibitor PF-46396 and the assembly cofactor inositol hexakisphosphate (IP6), determined by magic angle spinning (MAS) NMR spectroscopy. Our results reveal that although the two PF-46396 enantiomers exhibit distinct binding modes, they both possess similar anti-HIV potency.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Department of Chemistry, Boston University, 590 Commonwealth Ave, Boston, Massachusetts 02215, United States.
The cytosolic iron-sulfur cluster assembly (CIA) targeting complex maturates over 30 cytosolic and nuclear Fe-S proteins, raising the question of how a single complex recognizes such a diverse set of clients. The discovery of a C-terminal targeting complex recognition (TCR) peptide in up to 25% of CIA clients provided a clue to substrate specificity, yet the molecular and energetic basis for this interaction remained unresolved. By integrating computational and biochemical approaches, we show that the TCR peptide binds a conserved interface between the Cia1 and Cia2 subunits of the targeting complex, even in the absence of the Fe-S cluster.
View Article and Find Full Text PDFPLoS Pathog
September 2025
Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.
The parasitic protozoan Trypanosoma brucei has a single mitochondrial nucleoid, anchored to the basal body of the flagellum via the tripartite attachment complex (TAC). The detergent-insoluble TAC is essential for mitochondrial genome segregation during cytokinesis. The TAC assembles de novo in a directed way from the probasal body towards the kDNA.
View Article and Find Full Text PDFBiomacromolecules
September 2025
Division of Pharmacy and Optometry, Manchester Institute of Biotechnology, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, M13 9PL Manchester, U.K.
This study investigates how hydrophobic and hydrophilic modifications at the C-terminus of the base peptide, KFEFEFKFK (KbpK), affect the hydrogel macroscopic properties. By the incorporation of phenylalanine (F, hydrophobic) and lysine (K, hydrophilic) residues, four variants, KbpK-K, KbpK-F, KbpK-KF, and KbpK-FK, were designed and evaluated. pH-concentration phase diagrams and Fourier transform infrared confirmed clear links showing how peptide hydrophobicity and charge influence β-sheet formation and macroscopic phase behavior.
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