Aromatic Interactions Drive the Coupled Folding and Binding of the Intrinsically Disordered Sesbania mosaic Virus VPg Protein

Dixit, K and Karanth, NM and Nair, S and Kumari, K and Chakrabarti, KS and Savithri, HS and Sarma, SP (2020) Aromatic Interactions Drive the Coupled Folding and Binding of the Intrinsically Disordered Sesbania mosaic Virus VPg Protein. In: Biochemistry . (In Press)

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Abstract

The plant Sesbania mosaic virus a (+)-ssRNA sobemovirus VPg protein is intrinsically disordered in solution. For the virus life cycle, the VPg protein is essential for replication and for polyprotein processing that is carried out by a virus-encoded protease. The nuclear magnetic resonance (NMR)-derived tertiary structure of the protease-bound VPg shows it to have a novel tertiary structure with an α-β-β-β topology. The quaternary structure of the high-affinity protease-VPg complex (�27 kDa) has been determined using HADDOCK protocols with NMR (residual dipolar coupling, dihedral angle, and nuclear Overhauser enhancement) restraints and mutagenesis data as inputs. The geometry of the complex is in excellent agreement with long-range orientational restraints such as residual dipolar couplings and ring-current shifts. A "vein"of aromatic residues on the protease surface is pivotal for the folding of VPg via intermolecular edge-to-face �···�stacking between Trp271 and Trp368 of the protease and VPg, respectively, and for the CH···�interactions between Leu361 of VPg and Trp271 of the protease. The structure of the protease-VPg complex provides a molecular framework for predicting sites of important posttranslational modifications such as RNA linkage and phosphorylation and a better understanding of the coupled folding upon binding of intrinsically disordered proteins. The structural data presented here augment the limited structural data available on viral proteins, given their propensity for structural disorder. © 2020 American Chemical Society.

Item Type:	Journal Article
Publication:	Biochemistry
Publisher:	American Chemical Society
Additional Information:	Copyright to this article belongs to American Chemical Society
Keywords:	Binding sites; Digital storage; Dihedral angle; Life cycle; Proteins; Viruses, Aromatic interactions; Intrinsically disordered proteins; Nuclear magnetic resonance(NMR); Nuclear overhauser enhancement; Post-translational modifications; Quaternary structure; Residual dipolar couplings; Sesbania mosaic virus, Nuclear magnetic resonance
Department/Centre:	Division of Biological Sciences > Biochemistry Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	08 Jan 2021 09:46
Last Modified:	08 Jan 2021 09:46
URI:	http://eprints.iisc.ac.in/id/eprint/67544

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