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A Structural and Dynamic Analysis of the Partially Disordered Polymerase-Binding Domain in RSV Phosphoprotein
oleh: Christophe Cardone, Claire-Marie Caseau, Benjamin Bardiaux, Aurélien Thureaux, Marie Galloux, Monika Bajorek, Jean-François Eléouët, Marc Litaudon, François Bontems, Christina Sizun
Format: | Article |
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Diterbitkan: | MDPI AG 2021-08-01 |
Deskripsi
The phosphoprotein P of <i>Mononegavirales</i> (<i>MNV</i>) is an essential co-factor of the viral RNA polymerase L. Its prime function is to recruit L to the ribonucleocapsid composed of the viral genome encapsidated by the nucleoprotein N. <i>MNV</i> phosphoproteins often contain a high degree of disorder. In <i>Pneumoviridae</i> phosphoproteins, the only domain with well-defined structure is a small oligomerization domain (P<sub>OD</sub>). We previously characterized the differential disorder in respiratory syncytial virus (RSV) phosphoprotein by NMR. We showed that outside of RSV P<sub>OD</sub>, the intrinsically disordered N-and C-terminal regions displayed a structural and dynamic diversity ranging from random coil to high helical propensity. Here we provide additional insight into the dynamic behavior of P<sub>Cα</sub>, a domain that is C-terminal to P<sub>OD</sub> and constitutes the RSV L-binding region together with P<sub>OD</sub>. By using small phosphoprotein fragments centered on or adjacent to P<sub>OD</sub>, we obtained a structural picture of the P<sub>OD</sub>–P<sub>Cα</sub> region in solution, at the single residue level by NMR and at lower resolution by complementary biophysical methods. We probed P<sub>OD</sub>–P<sub>Cα</sub> inter-domain contacts and showed that small molecules were able to modify the dynamics of P<sub>Cα</sub>. These structural properties are fundamental to the peculiar binding mode of RSV phosphoprotein to L, where each of the four protomers binds to L in a different way.