PARPs and ADP-ribosylation-mediated biomolecular condensates: determinants, dynamics, and disease implications

Trends in Biochemical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Nucleotide-specific RNA conformations and dynamics within ribonucleoprotein condensates

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Abstract Ribonucleoprotein (RNP) condensates have distinct physiological and pathological significance, but the structure of RNA within them is not well understood. Using contrast-variation solution X-ray scattering, which discerns only structures protein-RNA complexes, alongside ensemble-based structural modeling we characterize conformational changes flexible poly-A, poly-U poly-C single stranded as it interacts with polybasic peptides, eventually forming condensed coacervate mixtures. At high salt concentrations, where macromolecular association weak, probe events that precede formation liquid-like droplets. Structural occur in reflect charge screening by peptides π − interactions bases basic residues. lower enhanced, poly-A phase separated RNP mixtures exhibit a broad scattering peak, suggesting subtle ordering. Coarse-grained molecular dynamics simulations are used to elucidate nucleotide-specific condensates. While adenine-rich behave like stable semidilute solutions, uracil-rich appear be compositionally fluctuating. This approach helps understand how sequence contributes grammar RNA-protein separation.

Language: Английский

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Poly(ADP-ribose) binding sites on collagen I fibrils for nucleating intrafibrillar bone mineral

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(8)

Published: Feb. 20, 2025

Bone calcification is essential for vertebrate life. The mechanism by which mineral ions are transported into collagen fibrils to induce intrafibrillar formation requires a calcium binding biopolymer that also has highly selective the fibril hole zones where begins, over other bone extracellular matrix components. Poly(ADP-ribose) (PAR) been shown be candidate this process and we show here PAR high affinity, conserved sites in type I C-terminal telopeptides. identification of these PAR-collagen gives insights chemical mechanisms underlying possible behind pathologies there dysfunctional calcification.

Language: Английский

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Phase Separation of FUS with Poly(ADP-ribosyl)ated PARP1 Is Controlled by Polyamines, Divalent Metal Cations, and Poly(ADP-ribose) Structure

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12445 - 12445

Published: Nov. 20, 2024

Fused in sarcoma (FUS) is involved the formation of nuclear biomolecular condensates associated with poly(ADP-ribose) [PAR] synthesis catalyzed by a DNA damage sensor such as PARP1. Here, we studied FUS microphase separation induced poly(ADP-ribosyl)ated PARP1

Language: Английский

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