期刊
NUCLEIC ACIDS RESEARCH
卷 50, 期 19, 页码 11243-11254出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkac841
关键词
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资金
- M.J. Murdock Charitable Trust
- National Institute of General Medical Sciences of the National Institutes of Health [P20GM103474, S10OD28650]
- Office of the Vice President for Research, Economic Development and Graduate Education
- NIH [R35GM134867]
- Amgen
- Montana State University Agricultural Experimental Station (USDA NIFA)
- MSU Office of the Vice President of Research Economic Development and Graduate Education
Viruses can interfere with cellular defense by expressing anti-CRISPR proteins. Research using HDX-MS and DSF experiments investigated the interaction between anti-CRISPR proteins and the CRISPR RNA-guided surveillance complex, revealing that AcrIF2 binding relies on enthalpic stabilization, while AcrIF9 uses an entropy driven reaction.
CRISPR RNA-guided detection and degradation of foreign DNA is a dynamic process. Viruses can interfere with this cellular defense by expressing small proteins called anti-CRISPRs. While structural models of anti-CRISPRs bound to their target complex provide static snapshots that inform mechanism, the dynamics and thermodynamics of these interactions are often overlooked. Here, we use hydrogen deuterium exchange-mass spectrometry (HDX-MS) and differential scanning fluorimetry (DSF) experiments to determine how anti-CRISPR binding impacts the conformational landscape of the type IF CRISPR RNA guided surveillance complex (Csy) upon binding of two different anti-CRISPR proteins (AcrIF9 and AcrIF2). The results demonstrate that AcrIF2 binding relies on enthalpic stabilization, whereas AcrIF9 uses an entropy driven reaction to bind the CRISPR RNA-guided surveillance complex. Collectively, this work reveals the thermodynamic basis and mechanistic versatility of anti-CRISPR-mediated immune suppression. More broadly, this work presents a striking example of how allosteric effectors are employed to regulate nucleoprotein complexes.
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