6M78

Aromatic interactions drive the coupled folding and binding of the intrinsically disordered Sesbania mosaic virus VPg protein

Summary for 6M78

• Entry DOI: 10.2210/pdb6m78/pdb
• Related: 1ZYO 6XLF
• Descriptor: Polyprotein (2 entities in total)
• Functional Keywords: viral-protein-genome-linked, complex, protease, plant viral protein, hydrolase
• Biological source: Sesbania mosaic virus; More
• Total number of polymer chains: 2
• Total formula weight: 41358.68

Authors

Dixit, K.,Karanth, N.M.,Nair, S.,Kumari, K.,Chakraborti, K.S.,Savithri, H.S.,Sarma, S.P. (deposition date: 2020-03-17, release date: 2021-01-27, Last modification date: 2024-11-13)

Primary citation

Dixit, K.,Karanth, N.M.,Nair, S.,Kumari, K.,Chakrabarti, K.S.,Savithri, H.S.,Sarma, S.P.
Aromatic Interactions Drive the Coupled Folding and Binding of the Intrinsically Disordered Sesbania mosaic Virus VPg Protein.
Biochemistry, 59:4663-4680, 2020

PubMed Abstract: The plant 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 π···π stacking between Trp and Trp of the protease and VPg, respectively, and for the CH···π interactions between Leu of VPg and Trp 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.

PubMed: 33269926
DOI: 10.1021/acs.biochem.0c00721

Experimental method

SOLUTION NMR