3TSI

Structure of the parainfluenza virus 5 (PIV5) hemagglutinin-neuraminidase (HN) stalk domain

Summary for 3TSI

• Entry DOI: 10.2210/pdb3tsi/pdb
• Descriptor: Hemagglutinin-neuraminidase (2 entities in total)
• Functional Keywords: four-helix bundle, four stranded coiled coil, 11-mer hydrophobic repeat, receptor binding protein, ectodomain, viral protein
• Biological source: Simian virus 5 (SV5)
• Cellular location: Virion membrane ; Single-pass type II membrane protein : P04850
• Total number of polymer chains: 4
• Total formula weight: 27394.78

Authors

Bose, S.,Welch, B.D.,Kors, C.A.,Yuan, P.,Jardetzky, T.S.,Lamb, R.A. (deposition date: 2011-09-13, release date: 2011-10-26, Last modification date: 2023-09-13)

Primary citation

Bose, S.,Welch, B.D.,Kors, C.A.,Yuan, P.,Jardetzky, T.S.,Lamb, R.A.
Structure and mutagenesis of the parainfluenza virus 5 hemagglutinin-neuraminidase stalk domain reveals a four-helix bundle and the role of the stalk in fusion promotion.
J.Virol., 85:12855-12866, 2011

PubMed Abstract: Paramyxovirus entry into cells requires the fusion protein (F) and a receptor binding protein (hemagglutinin-neuraminidase [HN], H, or G). The multifunctional HN protein of some paramyxoviruses, besides functioning as the receptor (sialic acid) binding protein (hemagglutinin activity) and the receptor-destroying protein (neuraminidase activity), enhances F activity, presumably by lowering the activation energy required for F to mediate fusion of viral and cellular membranes. Before or upon receptor binding by the HN globular head, F is believed to interact with the HN stalk. Unfortunately, until recently none of the receptor binding protein crystal structures have shown electron density for the stalk domain. Parainfluenza virus 5 (PIV5) HN exists as a noncovalent dimer-of-dimers on the surface of cells, linked by a single disulfide bond in the stalk. Here we present the crystal structure of the PIV5-HN stalk domain at a resolution of 2.65 Å, revealing a four-helix bundle (4HB) with an upper (N-terminal) straight region and a lower (C-terminal) supercoiled part. The hydrophobic core residues are a mix of an 11-mer repeat and a 3- to 4-heptad repeat. To functionally characterize the role of the HN stalk in F interactions and fusion, we designed mutants along the PIV5-HN stalk that are N-glycosylated to physically disrupt F-HN interactions. By extensive study of receptor binding, neuraminidase activity, oligomerization, and fusion-promoting functions of the mutant proteins, we found a correlation between the position of the N-glycosylation mutants on the stalk structure and their neuraminidase activities as well as their abilities to promote fusion.

PubMed: 21994464
DOI: 10.1128/JVI.06350-11

Experimental method

X-RAY DIFFRACTION (2.651 Å)