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TitleDMSO might impact ligand binding, capsid stability, and RNA interaction in viral preparations.
Journal, issue, pagesSci Rep, Vol. 14, Issue 1, Page 30408, Year 2024
Publish dateDec 6, 2024
AuthorsJiri Wald / Nikolaus Goessweiner-Mohr / Antonio Real-Hohn / Dieter Blaas / Thomas C Marlovits /
PubMed AbstractDimethyl 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 ...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.
External linksSci Rep / PubMed:39639094 / PubMed Central
MethodsEM (single particle)
Resolution1.76 - 1.96 Å
Structure data

50840

9fx1

EMDB-50840, PDB-9fx1:
CryoEM structure of RV-A89
Method: EM (single particle) / Resolution: 1.76 Å

50844

9fx9

EMDB-50844, PDB-9fx9:
CryoEM structure of RV-A89
Method: EM (single particle) / Resolution: 1.96 Å

Chemicals

ChemComp-DAO:
LAURIC ACID

ChemComp-HOH:
WATER

Source
  • human rhinovirus 89 atcc vr-1199
KeywordsVIRUS / RV-A89 / rhinovirus

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