title: 1H, 13C, and 15N resonance assignment of a 179 residue fragment of hepatitis C virus non-structural protein 5A.
abstract: Non-structural protein 5A (NS5A) plays an important role in the life cycle of hepatitis C virus. This proline-rich phosphoprotein is organized into three domains. Besides its role in virus replication and virus assembly, NS5A is involved in a variety of cellular regulation processes. Recent studies on domain 2 and 3 revealed that both belong to the class of intrinsically disordered proteins as they adopt a natively unfolded state. In particular, domain 2 together with its vicinal regions is responsible for NS5A's multiple interactions with other proteins necessary for virus persistence. The low chemical shift dispersion observed for instrinsically disordered proteins presents a challenge for NMR spectroscopy. Here we report sequential resonance assignment of a 179-residue fragment of NS5A, comprising the entire domain 2, using a set of sensitivity and resolution optimized 3D correlation experiments, as well as amino-acid-type editing in (1)H-(15)N correlation spectra. Our assignment reveals the presence of several segments with high propensity to form α-helical structure that may be of importance to the function of this protein fragment as a versatile interaction platform.
authors.affiliation: Institut de Biologie Structurale, Université Grenoble 1, 41 rue Jules Horowitz, 38027, Grenoble Cedex 1, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Feuerstein
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Solyom
authors.forename: Amine
authors.initials: A
authors.lastname: Aladağ
authors.forename: Silke
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.forename: Bernhard
authors.initials: B
authors.lastname: Brutscher
mesh_terms: D001665:Binding Sites; D016174:Hepacivirus / Q000737:chemistry*; D007554:Isotopes / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D017361:Viral Nonstructural Proteins / Q000737:chemistry*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D007554:Isotopes; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase