ArticleProtein science : a publication of the Protein Society2016
Using hydrogen deuterium exchange mass spectrometry to engineer optimized constructs for crystallization of protein complexes: Case study of PI4KIIIβ with Rab11.
Article in Protein science : a publication of the Protein Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Use of hydrogen deuterium exchange mass spectrometry in tandem with modern structural biology.The Biochemical journal · 2026Review
- Cryptosporidium PI(4)K inhibitor EDI048 is a gut-restricted parasiticidal agent to treat paediatric enteric cryptosporidiosis.Nature microbiology · 2024Article
- MgbioRxiv : the preprint server for biology · 2024Article
- Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein.Nature communications · 2023Article
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- Dynamics of protein kinases and pseudokinases by HDX-MS.Methods in enzymology · 2022Article
- Bipartite binding and partial inhibition links DEPTOR and mTOR in a mutually antagonistic embrace.eLife · 2021Article
- Review
- Bridging protein structure, dynamics, and function using hydrogen/deuterium-exchange mass spectrometry.Protein science : a publication of the Protein Society · 2020Review
- Characterization of the c10orf76-PI4KB complex and its necessity for Golgi PI4P levels and enterovirus replication.EMBO reports · 2020Article
- Dynamic structural biology at the protein membrane interface.The Journal of biological chemistry · 2019Review
- Phosphatidylinositol 4-kinase IIIβ (PI4KB) forms highly flexible heterocomplexes that include ACBD3, 14-3-3, and Rab11 proteins.Scientific reports · 2019Article
- Tracking Higher Order Protein Structure by Hydrogen-Deuterium Exchange Mass Spectrometry.Protein and peptide letters · 2019Review
- Endo-fucoidan hydrolases from glycoside hydrolase family 107 (GH107) display structural and mechanistic similarities to α-l-fucosidases from GH29.The Journal of biological chemistry · 2018Article
- Structural determinants of Rab11 activation by the guanine nucleotide exchange factor SH3BP5.Nature communications · 2018Article
- Article
- Ras Binder Induces a Modified Switch-II Pocket in GTP and GDP States.Cell chemical biology · 2017Article
- Structural insights and in vitro reconstitution of membrane targeting and activation of human PI4KB by the ACBD3 protein.Scientific reports · 2016Article
- Design and Structural Characterization of Potent and Selective Inhibitors of Phosphatidylinositol 4 Kinase IIIβ.Journal of medicinal chemistry · 2016Article
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Authors and funding
8 authors.
Funding
Abstract
The ability of proteins to bind and interact with protein partners plays fundamental roles in many cellular contexts. X-ray crystallography has been a powerful approach to understand protein-protein interactions; however, a challenge in the crystallization of proteins and their complexes is the presence of intrinsically disordered regions. In this article, we describe an application of hydrogen deuterium exchange mass spectrometry (HDX-MS) to identify dynamic regions within type III phosphatidylinositol 4 kinase beta (PI4KIIIβ) in complex with the GTPase Rab11. This information was then used to design deletions that allowed for the production of diffraction quality crystals. Importantly, we also used HDX-MS to verify that the new construct was properly folded, consistent with it being catalytically and functionally active. Structures of PI4KIIIβ in an Apo state and bound to the potent inhibitor BQR695 in complex with both GTPγS and GDP loaded Rab11 were determined. This hybrid HDX-MS/crystallographic strategy revealed novel aspects of the PI4KIIIβ-Rab11 complex, as well as the molecular mechanism of potency of a PI4K specific inhibitor (BQR695). This approach is widely applicable to protein-protein complexes, and is an excellent strategy to optimize constructs for high-resolution structural approaches.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.