New ProteomeXchange dataset PXD063379

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Dear ProteomeXchange subscriber, a new ProteomeXchange dataset is being announced. To see more information, click here:

https://proteomecentral.proteomexchange.org/dataset/PXD063379

Summary of dataset

Status: new
Identifier: PXD063379
HostingRepository: jPOST
Species: cellular organisms
Title: Cross-linking mass spectrometry and integrative structural modelling identifies compact conformation of DENV NS2B to NS3
Submitter: Radoslaw Sobota
LabHead: Radoslaw Sobota
Description: Dengue virus remains a public health threat. Dengue NS2B-NS3 proteins are prime antiviral drug targets and have been studied extensively. Here, we combine cross-linking mass spectrometry, molecular dynamics simulations and biochemical assays to identify NS2B-NS3 full length interactions. Using cross-linkers of different lengths as molecular rulers, we identified NS2B S48 as a key interacting residue that has not been previously reported. Molecular dynamics simulations modelled a compact conformation of NS2B to NS3 interaction with better agreement to cross-link data. In contrast, previously reported crystal structure indicated an elongated conformation with poor agreement to cross-link data. Mutation of NS2B S48 to alanine or lysine greatly reduces protease activity and disrupts the NS2B S48 binding pocket in the compact conformation. NS2B-NS3 cross-links were also found to be conserved across all four dengue serotypes. Our interdisciplinary approach reveals new key inte
racting residue and a compact conformation that can guide drug development against dengue.

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