5WKN

Crystal structure of the parainfluenza virus 5 nucleoprotein-phosphoprotein complex

5WKN の概要

• エントリーDOI: 10.2210/pdb5wkn/pdb
• 分子名称: Nucleoprotein, Phosphoprotein (3 entities in total)
• 機能のキーワード: paramyxovirus, nucleoprotein, phosphoprotein, conformational changes, viral protein
• 由来する生物種: Parainfluenza virus 5 (strain W3) (PIV5); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 89174.30

構造登録者

Aggarwal, M.,Leser, G.P.,Kors, C.A.,Lamb, R.A. (登録日: 2017-07-25, 公開日: 2017-12-13, 最終更新日: 2023-10-04)

主引用文献

Aggarwal, M.,Leser, G.P.,Kors, C.A.,Lamb, R.A.
Structure of the Paramyxovirus Parainfluenza Virus 5 Nucleoprotein in Complex with an Amino-Terminal Peptide of the Phosphoprotein.
J. Virol., 92:-, 2018

PubMed Abstract: Parainfluenza virus 5 (PIV5) belongs to the family , which consists of enveloped viruses with a nonsegmented negative-strand RNA genome encapsidated by the nucleoprotein (N). Paramyxovirus replication is regulated by the phosphoprotein (P) through protein-protein interactions with N and the RNA polymerase (L). The chaperone activity of P is essential to maintain the unassembled RNA-free form of N in order to prevent nonspecific RNA binding and premature N oligomerization. Here, we determined the crystal structure of unassembled PIV5 N in complex with a P peptide (NP) derived from the N terminus of P (P50) at 2.65 Å. The PIV5 NP consists of two domains: an N-terminal domain (NTD) and a C-terminal domain (CTD) separated by a hinge region. The cleft at the hinge region of RNA-bound PIV5 N was previously shown to be an RNA binding site. The NP structure shows that the P peptide binds to the CTD of N and extends toward the RNA binding site to inhibit N oligomerization and, hence, RNA binding. Binding of P peptide also keeps the PIV5 N in the open form. A molecular dynamics (MD) analysis of both the open and closed forms of N shows the flexibility of the CTD and the preference of the N protein to be in an open conformation. The gradual opening of the hinge region, to release the RNA, was also observed. Together, these results advance our knowledge of the conformational swapping of N required for the highly regulated paramyxovirus replication. Paramyxovirus replication is regulated by the interaction of P with N and L proteins. Here, we report the crystal structure of unassembled parainfluenza virus 5 (PIV5) N chaperoned with P peptide. Our results provide a detailed understanding of the binding of P to N. The conformational switching of N between closed and open forms during its initial interaction with P, as well as during RNA release, was analyzed. Our data also show the plasticity of the CTD and the importance of domain movement for conformational switching. The results improve our understanding of the mechanism of interchanging N conformations for RNA replication and release.

PubMed: 29237836
DOI: 10.1128/JVI.01304-17

実験手法

X-RAY DIFFRACTION (2.653 Å)