Phenotypic plasticity is the ability of individual genotypes to produce different phenotypes in response to environmental perturbations. We previously postulated how conformational noise emanating from conformational dynamics of intrinsically disordered proteins (IDPs) which is distinct from transcriptional noise, can contribute to phenotypic switching by rewiring the cellular protein interaction network. Since most transcription factors are IDPs, we posited that conformational noise is an integral component of transcriptional noise implying that IDPs may amplify total noise in the system either stochastically or in response to environmental changes. Here, we review progress in elucidating the details of the hypothesis. We highlight empirical evidence supporting the hypothesis, discuss conceptual advances that underscore its fundamental importance and implications, and identify areas for future investigations.
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http://dx.doi.org/10.1016/j.isci.2023.107109 | DOI Listing |
Nat Struct Mol Biol
January 2025
Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY, USA.
Following transcript release during intrinsic termination, Escherichia coli RNA polymerase (RNAP) often remains associated with DNA in a post-termination complex (PTC). RNAPs in PTCs are removed from the DNA by the SWI2/SNF2 adenosine triphosphatase (ATPase) RapA. Here we determined PTC structures on negatively supercoiled DNA and with RapA engaged to dislodge the PTC.
View Article and Find Full Text PDFAnal Chem
January 2025
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. China.
Hepatic fibrosis, a chronic liver response to injury with potential severe outcomes like cirrhosis and liver cancer, necessitates urgent noninvasive diagnostic techniques to halt disease progression. We herein for the first time developed a single-chain peptide probe targeting pathological collagen for in vivo magnetic resonance imaging (MRI) of hepatic fibrosis. The novel (GhypO) probe, distinguished by its unique monomeric conformation achieved through Pro to (2,4)-hydroxyproline (hyp) substitution and subsequent disruption of hydrogen bonding, exhibits selectivity for pathological collagen over its intact counterpart in connective tissues.
View Article and Find Full Text PDFBrief Bioinform
November 2024
School of Information Science and Technology, Northeast Normal University, 130117 Changchun, China.
Q Rev Biophys
December 2024
Preston M. Green Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Single-molecule orientation-localization microscopy (SMOLM) builds upon super-resolved localization microscopy by imaging orientations and rotational dynamics of individual molecules in addition to their positions. This added dimensionality provides unparalleled insights into nanoscale biophysical and biochemical processes, including the organization of actin networks, movement of molecular motors, conformations of DNA strands, growth and remodeling of amyloid aggregates, and composition changes within lipid membranes. In this review, we discuss recent innovations in SMOLM and cover three key aspects: (1) biophysical insights enabled by labeling strategies that endow fluorescent probes to bind to targets with orientation specificity; (2) advanced imaging techniques that leverage the physics of light-matter interactions and estimation theory to encode orientation information with high fidelity into microscope images; and (3) computational methods that ensure accurate and precise data analysis and interpretation, even in the presence of severe shot noise.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China.
Observing chemical reactions in complex structures such as zeolites involves a major challenge in precisely capturing single-molecule behavior at ultra-high spatial resolutions. To address this, a sophisticated deep learning framework tailored has been developed for integrated Differential Phase Contrast Scanning Transmission Electron Microscopy (iDPC-STEM) imaging under low-dose conditions. The framework utilizes a denoising super-resolution model (Denoising Inference Variational Autoencoder Super-Resolution (DIVAESR)) to effectively mitigate shot noise and thereby obtain substantially clearer atomic-resolved iDPC-STEM images.
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