3T1E

The structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a 4-helix bundle stalk

Summary for 3T1E

• Entry DOI: 10.2210/pdb3t1e/pdb
• Descriptor: Hemagglutinin-neuraminidase (1 entity in total)
• Functional Keywords: beta-propeller, 4 helix bundle, hemagglutinin, neuraminidase, membrane protein, ectodomain, hydrolase
• Biological source: Newcastle disease virus (NDV)
• Cellular location: Virion membrane; Single-pass type II membrane protein (Potential): P12554
• Total number of polymer chains: 4
• Total formula weight: 234814.94

Authors

Yuan, P.,Swanson, K.,Leser, G.P.,Paterson, R.G.,Lamb, R.A.,Jardetzky, T.S. (deposition date: 2011-07-21, release date: 2011-09-07, Last modification date: 2024-11-27)

Primary citation

Yuan, P.,Swanson, K.A.,Leser, G.P.,Paterson, R.G.,Lamb, R.A.,Jardetzky, T.S.
Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk.
Proc.Natl.Acad.Sci.USA, 108:14920-14925, 2011

PubMed Abstract: The paramyxovirus hemagglutinin-neuraminidase (HN) protein plays multiple roles in viral entry and egress, including binding to sialic acid receptors, activating the fusion (F) protein to activate membrane fusion and viral entry, and cleaving sialic acid from carbohydrate chains. HN is an oligomeric integral membrane protein consisting of an N-terminal transmembrane domain, a stalk region, and an enzymatically active neuraminidase (NA) domain. Structures of the HN NA domains have been solved previously; however, the structure of the stalk region has remained elusive. The stalk region contains specificity determinants for F interactions and activation, underlying the requirement for homotypic F and HN interactions in viral entry. Mutations of the Newcastle disease virus HN stalk region have been shown to affect both F activation and NA activities, but a structural basis for understanding these dual affects on HN functions has been lacking. Here, we report the structure of the Newcastle disease virus HN ectodomain, revealing dimers of NA domain dimers flanking the N-terminal stalk domain. The stalk forms a parallel tetrameric coiled-coil bundle (4HB) that allows classification of extensive mutational data, providing insight into the functional roles of the stalk region. Mutations that affect both F activation and NA activities map predominantly to the 4HB hydrophobic core, whereas mutations that affect only F-protein activation map primarily to the 4HB surface. Two of four NA domains interact with the 4HB stalk, and residues at this interface in both the stalk and NA domain have been implicated in HN function.

PubMed: 21873198
DOI: 10.1073/pnas.1111691108

Experimental method

X-RAY DIFFRACTION (3.301 Å)