Journal Article

PUBDB-2025-00296

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png DMSO might impact ligand binding, capsid stability, and RNA interaction in viral preparations

Wald, J. (Corresponding author)Extern*CSSB*DESY* ; Goessweiner-Mohr, N. ; Real-Hohn, A. ; Blaas, D. (Corresponding author) ; Marlovits, T. (Corresponding author)CSSB*DESY*

2024
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41598-024-81789-x  doi:10.3204/PUBDB-2025-00296

Abstract: Dimethyl sulfoxide (DMSO) is a widely used solvent in drug research. However, recent studies indicate that even at low concentration DMSO might cause structural changes of proteins and RNA. The pyrazolopyrimidine antiviral OBR-5-340 dissolved in DMSO inhibits rhinovirus-B5 infection yet is inactive against RV-A89. This is consistent with our structural observation that OBR-5-340 is only visible at the pocket factor site in rhinovirus-B5 and not in RV-A89, where the hydrophobic pocket is collapsed. Here, we analyze the impact of DMSO in RV-A89 by high-resolution cryo-electron microscopy. Our 1.76 Å cryo-EM reconstruction of RV-A89 in plain buffer, without DMSO, reveals that the pocket-factor binding site is occupied by myristate and that the previously observed local heterogeneity at protein–RNA interfaces is absent. These findings suggest that DMSO elutes the pocket factor, leading to a collapse of the hydrophobic pocket of RV-A89. Consequently, the conformational heterogeneity observed at the RNA-protein interface in the presence of DMSO likely results from increased capsid flexibility due to the absence of the pocket factor and DMSO-induced affinity modifications. This local asymmetry may promote a directional release of the RNA genome during infection.

Note: DFG grant numbers INST152/772-1,152/774-1, 152/775-1, 152/776-1 and 152/777-1 FUGG.

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Contributing Institute(s):

1. Strukturelle Mikrobiologie CSSB (FS-CS)
2. CSSB-UKE-TM (CSSB-UKE-TM)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)

Experiment(s):

1. No specific instrument

Appears in the scientific report 2024

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