Targeting the N-Terminus Domain of the Coronavirus Nucleocapsid Protein Induces Abnormal Oligomerization via Allosteric Modulation

Hsu J, Chen J, Lin S, Hong J, Chen Y, Jeng U, Luo S, Hou M, Frontiers in Molecular Biosciences 9 (2022) DOI

SASDNF6 – full-length MERS CoV N -protein complexed with 5-propoxy-1H-indole (P4-1 compound)

Nucleoprotein
5-(Propoxy)-1H-indole
MWexperimental 550 kDa
MWexpected 550 kDa
VPorod 896 nm3
log I(s) 6.43×10-2 6.43×10-3 6.43×10-4 6.43×10-5
Nucleoprotein 5-(Propoxy)-1H-indole small angle scattering data  s, nm-1
ln I(s)
Nucleoprotein 5-(Propoxy)-1H-indole Guinier plot ln 6.43×10-2 Rg: 6.4 nm 0 (6.4 nm)-2 s2
(sRg)2I(s)/I(0)
Nucleoprotein 5-(Propoxy)-1H-indole Kratky plot 1.104 0 3 sRg
p(r)
Nucleoprotein 5-(Propoxy)-1H-indole pair distance distribution function Rg: 6.5 nm 0 Dmax: 22.0 nm

Data validation


Fits and models


log I(s)
 s, nm-1
Nucleoprotein 5-(Propoxy)-1H-indole CORAL model

Synchrotron SAXS data from solutions of full-length MERS CoV N -protein complexed with 5-propoxy-1H-indole (P4-1 compound) in 50 mM Tris-HCl, 150 mM NaCl, pH 8.5 were collected on the 23A beam line at the Taiwan Photon Source, NSRRC storage ring (Hsinchu, Taiwan) using a Pilatus 1M-F detector at a sample-detector distance of 2.5 m and at a wavelength of λ = 0.08 nm (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). In-line size-exclusion chromatography (SEC) SAS was employed. The SEC parameters were as follows: A 300.00 μl sample at 2 mg/ml was injected at a 0.02 ml/min flow rate onto a Agilent Bio SEC-3, 300 Å column at 14.9°C. 36 successive 30 second frames were collected. The data were normalized to the intensity of the transmitted beam and radially averaged; the scattering of the solvent-blank was subtracted.

Nucleoprotein
Mol. type   Protein
Organism   Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
Olig. state   Dodecamer
Mon. MW   45.7 kDa
 
UniProt   K9N4V7 (1-411)
Sequence   FASTA
 
5-(Propoxy)-1H-indole
Mol. type   Other
Olig. state   Dodecamer
Mon. MW   0.2 kDa
Chemical formula