Structural highlights
Function
[HN_SV5] Attaches the virus to sialic acid-containing cell receptors and thereby initiating infection. Binding of HN protein to the receptor induces a conformational change that allows the F protein to trigger virion/cell membranes fusion (By similarity). Neuraminidase activity ensures the efficient spread of the virus by dissociating the mature virions from the neuraminic acid containing glycoproteins (By similarity).
Publication Abstract from PubMed
Paramyxovirus entry into cells requires the fusion protein (F) and a receptor binding protein (HN, H or G). The multifunctional hemagglutinin-neuraminidase (HN) protein of some paramyxoviruses, besides functioning as the receptor (sialic acid) binding protein (hemagglutinin activity) and the receptor-destroying protein (neuraminidase activity), enhances fusion protein (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 non-covalent 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 A 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 3-4 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.
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.,Bose S, Welch BD, Kors CA, Yuan P, Jardetzky TS, Lamb RA J Virol. 2011 Oct 12. PMID:21994464[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bose S, Welch BD, Kors CA, Yuan P, Jardetzky TS, Lamb RA. 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. 2011 Oct 12. PMID:21994464 doi:10.1128/JVI.06350-11
