6Z0O

Structure of Affimer-NP bound to Crimean-Congo Haemorrhagic Fever Virus Nucleocapsid Protein

Summary for 6Z0O

• Entry DOI: 10.2210/pdb6z0o/pdb
• Related: 4AKL
• Descriptor: Nucleocapsid, Affimer-NP (3 entities in total)
• Functional Keywords: crimean-congo hemorrhagic fever virus nucleoprotein, affimer-np, complex, high-affinity, anti-viral, rna-binding, viral protein
• Biological source: Crimean-Congo hemorrhagic fever orthonairovirus; More
• Total number of polymer chains: 4
• Total formula weight: 129805.86

Authors

Alvarez-Rodriguez, B.,Tiede, C.,Trinh, C.,Tomlinson, D.,Edwards, T.A.,Barr, J.N. (deposition date: 2020-05-10, release date: 2020-05-27, Last modification date: 2024-01-24)

Primary citation

Alvarez-Rodriguez, B.,Tiede, C.,Hoste, A.C.R.,Surtees, R.A.,Trinh, C.H.,Slack, G.S.,Chamberlain, J.,Hewson, R.,Fresco, A.,Sastre, P.,Tomlinson, D.C.,Millner, P.A.,Edwards, T.A.,Barr, J.N.
Characterization and applications of a Crimean-Congo hemorrhagic fever virus nucleoprotein-specific Affimer: Inhibitory effects in viral replication and development of colorimetric diagnostic tests.
Plos Negl Trop Dis, 14:e0008364-e0008364, 2020

PubMed Abstract: Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) is one of the most widespread medically important arboviruses, causing human infections that result in mortality rates of up to 60%. We describe the selection of a high-affinity small protein (Affimer-NP) that binds specifically to the nucleoprotein (NP) of CCHFV. We demonstrate the interference of Affimer-NP in the RNA-binding function of CCHFV NP using fluorescence anisotropy, and its inhibitory effects on CCHFV gene expression in mammalian cells using a mini-genome system. Solution of the crystallographic structure of the complex formed by these two molecules at 2.84 Å resolution revealed the structural basis for this interference, with the Affimer-NP binding site positioned at the critical NP oligomerization interface. Finally, we validate the in vitro application of Affimer-NP for the development of enzyme-linked immunosorbent and lateral flow assays, presenting the first published point-of-care format test able to detect recombinant CCHFV NP in spiked human and animal sera.

PubMed: 32492018
DOI: 10.1371/journal.pntd.0008364

Experimental method

X-RAY DIFFRACTION (2.5974 Å)