Details

Autor(en) / Beteiligte

• Sarto, Carolina
• Kaufman, Sergio B.
• Estrin, Dario A.
• Arrar, Mehrnoosh

Titel

Nucleotide-dependent dynamics of the Dengue NS3 helicase

Ist Teil von

• Biochimica et biophysica acta. Proteins and proteomics, 2020-08, Vol.1868 (8), p.140441, Article 140441

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Dengue represents a substantial public health burden, particularly in low-resource countries. Non-structural protein 3 (NS3) is a multifunctional protein critical in the virus life cycle and has been identified as a promising anti-viral drug target. Despite recent crystallographic studies of the NS3 helicase domain, only subtle structural nucleotide-dependent differences have been identified, such that its coupled ATPase and helicase activities remain mechanistically unclear. Here we use molecular dynamics simulations to explore the nucleotide-dependent conformational landscape of the Dengue virus NS3 helicase and identify substantial changes in the protein flexibility during the ATP hydrolysis cycle. We relate these changes to the RNA-protein interactions and proposed translocation models for other monomeric helicases. Furthermore, we report a novel open-loop conformation with a likely escape route for Pi after hydrolysis, providing new insight into the conformational changes that underlie the ATPase activity of NS3. •Novel open-loop conformation identified in molecular dynamics simulations•Open-loop conformation provides a plausible exit pathway for Pi•Simulations of RNA-bound NS3 helicase show alternation between flexible and rigid states.