Mechanism of a Mutation in Non-Structural Protein 1 Including High Pathogenicity of Avian Influenza Virus H5N1
加藤, 有介 The Institute for Enzyme Research, Tokushima University|Institute for Health Sciences, Tokushima Bunri University KAKEN研究者をさがす
福井, 清 The Institute for Enzyme Research, Tokushima University 徳島大学 教育研究者総覧 KAKEN研究者をさがす
鈴木, 和男 Asia International Institute of Infectious Disease Control, and Department of Health Protection, Graduate School of Medicine, Teikyo University
non-structural protein 1
Avian influenza H5N1 has shown high mortality rate in human. Non-structural protein 1 (NS1) is a virulence factor of H5N1. Mutation at the 42nd residue within the RNA-binding domain (RBD) of NS1 dramatically changes the degree of pathogenicity of H5N1 in mice. We here studied the impact of this mutation on the function of RBD, and found that RBD with serine at the 42th residue binds doublestranded RNA (dsRNA), whereas that with proline at the 42th residue does not. Analysis of structural models of the RBD proteins with S42 and P42 suggested remarkable difference in the structure of the dsRNA-binding interface, whereas structural analysis by analytical gel filtration and CD measurements did not indicate difference between those RBD proteins. Our results suggest that the single amino acid replacement induces a minor, but global structural change leading to the loss of function of NS1 thereby the change in the degree of pathogenicity.
Protein and Peptide Letters
Running Title : NS1 Mechanism of High Pathogenicity of H5N1
The published manuscript is available at EurekaSelect via http://www.eurekaselect.com/openurl/content.php?genre=article&doi=10.2174/0929866523666160204124406.
Protein and Peptide Letters (2016) Vol.23 Issue4 p.372-378
LID201704072001.pdf 2.05 MB