In duplex DNA, A-T and G-C form Watson-Crick base pairs, and Hoogsteen pairing only dominates upon protein binding or DNA damage. Using NMR, we show that an A-T Hoogsteen base pair previously observed in crystal structures of transposon DNA hairpins bound to TnpA protein forms in solution even in the absence of TnpA. This Hoogsteen base pair, located adjacent to a dinucleotide apical loop, exists in dynamic equilibrium with a minor Watson-Crick conformation (population ∼11% and lifetime ∼55 µs).
View Article and Find Full Text PDFPediatric liver transplantation (PLT) is a life-saving procedure for children with end-stage liver disease. However, post-transplant monitoring, particularly the diagnosis and prognosis of complications such as allograft fibrosis, remains challenging. Traditionally, liver biopsy has been the gold standard for assessing allograft fibrosis, despite its invasive nature and inherent procedural risks.
View Article and Find Full Text PDFBiol Rev Camb Philos Soc
November 2024
Mitochondria are dynamic and plastic, undergoing continuous fission and fusion and rearrangement of their bioenergetic sub-compartments called cristae. These fascinating processes are best understood in animal and fungal models, which are taxonomically grouped together in the expansive Opisthokonta supergroup. In opisthokonts, crista remodelling and inner membrane fusion are linked by dynamin-related proteins (DRPs).
View Article and Find Full Text PDFCurr Opin Struct Biol
December 2024
The energy cost accompanying changes in the structures of nucleic acids when they bind partner molecules is a significant but underappreciated thermodynamic contribution to binding affinity and specificity. This review highlights recent advances in measuring conformational penalties and determining their contribution to the recognition, folding, and regulatory activities of nucleic acids. Notable progress includes methods for measuring and structurally characterizing lowly populated conformational states, obtaining ensemble information in high throughput, for large macromolecular assemblies, and in complex cellular environments.
View Article and Find Full Text PDFFolded RNAs contain tertiary contact motifs whose structures and energetics are conserved across different RNAs. The transferable properties of RNA motifs simplify the RNA folding problem, but measuring energetic and conformational properties of many motifs remains a challenge. Here, we use a high-throughput thermodynamic approach to investigate how sequence changes alter the binding properties of naturally occurring motifs, the GAAA tetraloop • tetraloop receptor (TLR) interactions.
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