TY  - JOUR
AU  - Wald, Jiri
AU  - Goessweiner-Mohr, Nikolaus
AU  - Real-Hohn, Antonio
AU  - Blaas, Dieter
AU  - Marlovits, Thomas
TI  - DMSO might impact ligand binding, capsid stability, and RNA interaction in viral preparations
JO  - Scientific reports
VL  - 14
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Springer Nature
M1  - PUBDB-2025-00296
SP  - 30408
PY  - 2024
N1  - DFG grant numbers INST152/772-1,152/774-1, 152/775-1, 152/776-1 and 152/777-1 FUGG.
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 39639094
UR  - <Go to ISI:>//WOS:001371833500006
DO  - DOI:10.1038/s41598-024-81789-x
UR  - https://bib-pubdb1.desy.de/record/622258
ER  -