4MZE

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

Summary for 4MZE

• Entry DOI: 10.2210/pdb4mze/pdb
• Related: 4MZA
• Descriptor: Hemagglutinin-neuraminidase, DI(HYDROXYETHYL)ETHER, SULFATE ION, ... (12 entities in total)
• Functional Keywords: viral envelope protein, viral fusion protein, hydrolase
• Biological source: Human parainfluenza 3 virus (HPIV-3)
• Cellular location: Virion membrane ; Single-pass type II membrane protein : P08492
• Total number of polymer chains: 2
• Total formula weight: 103169.88

Authors

Xu, R.,Wilson, I.A. (deposition date: 2013-09-30, release date: 2013-11-06, Last modification date: 2020-07-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)