Hydrogen–Deuterium Exchange Mass Spectrometry Reveals Mechanistic Insights into RNA Oligonucleotide-Mediated Inhibition of TDP-43 Aggregation

Thomas · 2024

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Description

Researchers use in 2024 hydrogen-deuterium exchange mass spectrometry to watch how RNA strands stop a brain protein from clumping. Clumps of TDP-43 mark several degenerative brain diseases. RNA binding is known to block clumping, but the shape changes behind that guard were unknown.

Exchange patterns show RNA shields the protein's RNA-grabbing domains and the linker between them. At high salt, one natural RNA sequence loses its guard while a repeat sequence keeps it. The loss aligns with a salt-driven shape shift in the bound protein. Domain contact changes emerge as the key mechanism. The work may guide RNA-based drugs that keep the protein soluble in diseased brains.

Catalog record

CREATORThomas
YEAR2024
COLLECTIONPAPERS
FORMATTXT
FILE SIZE52 KB
VERSION1.0
LICENSECC BY 4.0
RIGHTSCC BY
SOURCEEurope PMC

Source: https://europepmc.org/articles/PMC11638948

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