4OPA

X-ray structure of H6N6-NS1 delta(80-84) mutant

4OPA の概要

• エントリーDOI: 10.2210/pdb4opa/pdb
• 関連するPDBエントリー: 3F5T 4OPH
• 分子名称: Nonstructural protein 1 (2 entities in total)
• 機能のキーワード: alpha-helix beta-crescent fold, interferon antagonist, phosphorylation, sumoylation, nucleus, viral protein
• 由来する生物種: Influenza A virus
• 細胞内の位置: Host nucleus: Q20NS3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 50972.14

構造登録者

Carrillo, B. (登録日: 2014-02-05, 公開日: 2014-02-19, 最終更新日: 2023-09-20)

主引用文献

Carrillo, B.,Choi, J.M.,Bornholdt, Z.A.,Sankaran, B.,Rice, A.P.,Prasad, B.V.
The Influenza A Virus Protein NS1 Displays Structural Polymorphism.
J.Virol., 88:4113-4122, 2014

PubMed Abstract: NS1 of influenza A virus is a potent antagonist of host antiviral interferon responses. This multifunctional protein with two distinctive domains, an RNA-binding domain (RBD) and an effector domain (ED) separated by a linker region (LR), is implicated in replication, pathogenesis, and host range. Although the structures of individual domains of NS1 from different strains of influenza viruses have been reported, the only structure of full-length NS1 available to date is from an H5N1 strain (A/Vietnam/1203/2004). By carrying out crystallographic analyses of full-length H6N6-NS1 (A/blue-winged teal/MN/993/1980) and an LR deletion mutant, combined with mutational analysis, we show here that these full-length NS1 structures provide an exquisite structural sampling of various conformational states of NS1 that based on the orientation of the ED with respect to RBD can be summarized as "open," "semi-open," and "closed" conformations. Our studies show that preference for these states is clearly dictated by determinants such as linker length, residue composition at position 71, and a mechanical hinge, providing a structural basis for strain-dependent functional variations in NS1. Because of the flexibility inherent in the LR, any particular NS1 could sample the conformational space around these states to engage ED in different quaternary interactions so that it may participate in specific protein-protein or protein-RNA interactions to allow for the known multifunctionality of NS1. We propose that such conformational plasticity provides a mechanism for autoregulating NS1 functions, depending on its temporal distribution, posttranslational modifications, and nuclear or cellular localization, during the course of virus infection.

PubMed: 24478439
DOI: 10.1128/JVI.03692-13

実験手法

X-RAY DIFFRACTION (2.7 Å)