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Prostate apoptosis response factor-4 (Par-4) is a pro-apoptotic and tumor-suppressive protein. A highly conserved heptad repeat sequence at the Par-4 C-terminus suggests the presence of a leucine zipper (LZ). This C-terminal region is essential for Par-4 self-association and interaction with various effector proteins. We have used nuclear magnetic resonance (NMR) spectroscopy to fully assign the chemical shift resonances of a peptide comprising the LZ domain of Par-4 at neutral pH. Further, we have investigated the properties of the Par-4 LZ domain and two point mutants under a variety of conditions using NMR, circular dichroism (CD), light scattering, and bioinformatics. Results indicate an environment-dependent conformational equilibrium between a partially ordered monomer (POM) and a predominantly coiled coil dimer (CCD). The combination of techniques used allows the time scales of the equilibrium to be probed and also helps to identify features of the amino acid sequence that may influence the equilibrium.
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http://dx.doi.org/10.1002/prot.22752 | DOI Listing |
Spectrochim Acta A Mol Biomol Spectrosc
September 2025
Department of Chemistry, University of Copenhagen, Universitetsparken 5, Copenhagen-Ø, DK-2100, Denmark. Electronic address:
Absorption spectra of neopentyl alcohol and pinacolyl alcohol are recorded in the gas phase at room temperature and equilibrium conditions. A combination of conventional Fourier transform spectroscopy and cavity ringdown spectroscopy is used to cover the spectral OH-stretching regions, Δv=1-5. The conformer distributions of the alcohols are determined from the recorded spectra combined with transition intensities calculated with a reduced dimensional local mode model.
View Article and Find Full Text PDFUnlabelled: The misfolding and aggregation of α-synuclein is a central molecular event in the etiology of Parkinson's disease and related disorders. α-Synuclein misfolding and pathology are both concentration-dependent, but it is not clear precisely how changes in concentration alter the folding landscape within cells. Whereas most conventional structural biology approaches offer limited resolution in living systems, deep mutational scanning can offer insight into the folding state of a protein in living cells, and we apply this method to probe concentration-dependent changes in the folding of α-synuclein in a popular yeast model of pathology.
View Article and Find Full Text PDFJ Biol Chem
September 2025
Molecular Structure of Cell Signalling Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, United Kingdom. Electronic address:
The SspH/IpaH family of novel E3 ligases (NELs) are found in a number of Gram-negative bacteria and are used to target host enzymes for degradation to support pathogenesis. These E3 enzymes are autoinhibited in the absence of substrate and different models for release of autoinhibition have been suggested. However, many of the molecular details of individual steps during the ubiquitin transfer reaction remain unknown.
View Article and Find Full Text PDFJ Chem Phys
September 2025
Chemistry and Forensic Science, School of Natural Sciences, University of Kent, Park Wood Rd, Canterbury CT2 7NH, United Kingdom.
Self-assembled monolayers (SAMs) of alkanethiols on gold surfaces are important for various technological applications, such as electroanalytical sensors, organic electronic devices, and catalysts. However, providing a consistent computational description of the unique structural features of these SAMs, such as adsorption patterns, chain conformations, and superlattice arrangements, is challenging, particularly within a versatile computational framework that can simulate both the structural features of these systems and their irradiation-driven chemical transformations. This study systematically analyzes molecular mechanics force field parameters for bonded and nonbonded (van der Waals and electrostatic) interactions in alkanethiol SAMs with different terminal groups.
View Article and Find Full Text PDFRSC Adv
August 2025
School of Instrumentation and Optoelectronic Engineering, Beihang University Beijing 100191 China
To investigate the anti-relaxation performance of FOTS-modified OTS coatings on the inner walls of cesium (Cs) atomic cell, this study employs molecular dynamics (MD) simulations to explore the self-assembly process of FOTS-modified OTS molecular chains on the SiO (001) surface and evaluates the effects of FOTS chain amounts, water molecule content, and temperature on the diffusion behavior of Cs atoms. Results show that the optimized interface model of the FOTS-modified OTS coating and SiO substrate achieves thermodynamic and energetic equilibrium under the conditions of 25 °C and 2000 ps. The film formation process of FOTS-modified OTS chains on SiO surfaces involves three distinct stages: initial anchoring, conformational rearrangement, and structural relaxation and equilibrium configuration.
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