ArticleBiophysical journal2015
The Disordered Region of the HCV Protein NS5A: Conformational Dynamics, SH3 Binding, and Phosphorylation.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Predicting the sequence-dependent backbone dynamics of intrinsically disordered proteins.eLife · 2024Article
- Predicting the Sequence-Dependent Backbone Dynamics of Intrinsically Disordered Proteins.bioRxiv : the preprint server for biology · 2024Article
- G3BP/Rin-Binding Motifs Inserted into Flexible Regions of nsP2 Support RNA Replication of Chikungunya Virus.Journal of virology · 2022Article
- Regulatory Role of Phospholipids in Hepatitis C Virus Replication and Protein Function.Pathogens (Basel, Switzerland) · 2022Review
- Hyper-phosphorylation of nsp2-related proteins of porcine reproductive and respiratory syndrome virus.Virology · 2020Article
- Generation of the configurational ensemble of an intrinsically disordered protein from unbiased molecular dynamics simulation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Phosphorylated tyrosine 93 of hepatitis C virus nonstructural protein 5A is essential for interaction with host c-Src and efficient viral replication.The Journal of biological chemistry · 2019Article
- Review
- PreSMo Target-Binding Signatures in Intrinsically Disordered Proteins.Molecules and cells · 2018Review
- Modulation of the HIV nucleocapsid dynamics finely tunes its RNA-binding properties during virion genesis.Nucleic acids research · 2018Article
- NMR reveals the intrinsically disordered domain 2 of NS5A protein as an allosteric regulator of the hepatitis C virus RNA polymerase NS5B.The Journal of biological chemistry · 2017Article
- Optimized fast mixing device for real-time NMR applications.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2017Article
- Small heterodimer partner 1 directly interacts with NS5A viral protein and has a key role in HCV related liver cell transformation.Oncotarget · 2016Article
- IDPs: Less Disordered and More Ordered than Expected.Biophysical journal · 2015Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intrinsically disordered proteins (IDPs) perform their physiological role without possessing a well-defined three-dimensional structure. Still, residual structure and conformational dynamics of IDPs are crucial for the mechanisms underlying their functions. For example, regions of transient secondary structure are often involved in molecular recognition, with the structure being stabilized (or not) upon binding. Long-range interactions, on the other hand, determine the hydrodynamic radius of the IDP, and thus the distance over which the protein can catch binding partners via so-called fly-casting mechanisms. The modulation of long-range interactions also presents a convenient way of fine-tuning the protein's interaction network, by making binding sites more or less accessible. Here we studied, mainly by nuclear magnetic resonance spectroscopy, residual secondary structure and long-range interactions in nonstructural protein 5A (NS5A) from hepatitis C virus (HCV), a typical viral IDP with multiple functions during the viral life cycle. NS5A comprises an N-terminal folded domain, followed by a large (∼250-residue) disordered C-terminal part. Comparing nuclear magnetic resonance spectra of full-length NS5A with those of a protein construct composed of only the C-terminal residues 191-447 (NS5A-D2D3) allowed us to conclude that there is no significant interaction between the globular and disordered parts of NS5A. NS5A-D2D3, despite its overall high flexibility, shows a large extent of local residual (α-helical and β-turn) structure, as well as a network of electrostatic long-range interactions. Furthermore, we could demonstrate that these long-range interactions become modulated upon binding to the host protein Bin1, as well as after NS5A phosphorylation by CK2. As the charged peptide regions involved in these interactions are well conserved among the different HCV genotypes, these transient long-range interactions may be important for some of the functions of NS5A over the course of the HCV life cycle.
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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.