4MZE

Crystal structure of hPIV3 hemagglutinin-neuraminidase, H552Q/Q559R mutant

4MZE の概要

• エントリーDOI: 10.2210/pdb4mze/pdb
• 関連するPDBエントリー: 4MZA
• 分子名称: Hemagglutinin-neuraminidase, DI(HYDROXYETHYL)ETHER, SULFATE ION, ... (12 entities in total)
• 機能のキーワード: viral envelope protein, viral fusion protein, hydrolase
• 由来する生物種: Human parainfluenza 3 virus (HPIV-3)
• 細胞内の位置: Virion membrane ; Single-pass type II membrane protein : P08492
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 103169.88

構造登録者

Xu, R.,Wilson, I.A. (登録日: 2013-09-30, 公開日: 2013-11-06, 最終更新日: 2024-11-20)

主引用文献

Xu, R.,Palmer, S.G.,Porotto, M.,Palermo, L.M.,Niewiesk, S.,Wilson, I.A.,Moscona, A.
Interaction between the hemagglutinin-neuraminidase and fusion glycoproteins of human parainfluenza virus type III regulates viral growth in vivo.
MBio, 4:e00803-e00813, 2013

PubMed Abstract: Paramyxoviruses, enveloped RNA viruses that include human parainfluenza virus type 3 (HPIV3), cause the majority of childhood viral pneumonia. HPIV3 infection starts when the viral receptor-binding protein engages sialic acid receptors in the lung and the viral envelope fuses with the target cell membrane. Fusion/entry requires interaction between two viral surface glycoproteins: tetrameric hemagglutinin-neuraminidase (HN) and fusion protein (F). In this report, we define structural correlates of the HN features that permit infection in vivo. We have shown that viruses with an HN-F that promotes growth in cultured immortalized cells are impaired in differentiated human airway epithelial cell cultures (HAE) and in vivo and evolve in HAE into viable viruses with less fusogenic HN-F. In this report, we identify specific structural features of the HN dimer interface that modulate HN-F interaction and fusion triggering and directly impact infection. Crystal structures of HN, which promotes viral growth in vivo, show a diminished interface in the HN dimer compared to the reference strain's HN, consistent with biochemical and biological data indicating decreased dimerization and decreased interaction with F protein. The crystallographic data suggest a structural explanation for the HN's altered ability to activate F and reveal properties that are critical for infection in vivo.

PubMed: 24149514
DOI: 10.1128/mBio.00803-13

実験手法

X-RAY DIFFRACTION (1.8 Å)