PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Protein Folding and Misfolding: It's the Journey, Not the Destination
March 2015
CCR5 and HIV Infection
January 2015
HIV/AIDS: Pre-fusion Env Exposed
January 2015
HIV/AIDS: Slide to Enter
January 2015
Updating ModBase
January 2015
Power in Numbers
August 2014
Quorum Sensing: A Groovy New Component
August 2014
Bacterial CDI Toxins
June 2014
Immunity: One Antibody to Rule Them All
June 2014
Virology: A Bat Influenza Hemagglutinin
March 2014
Virology: Making Sensitive Magic
March 2014
Virology: Visualizing Cyanophage Assembly
March 2014
Virology: Zeroing in on HBV Egress
March 2014
March 2014
Cas4 Nuclease and Bacterial Immunity
February 2014
Microbial Pathogenesis: A GNAT from Pseudomonas
February 2014
Microbial Pathogenesis: Targeting Drug Resistance in Mycobacterium tuberculosis
February 2014
Microbiome: The Dynamics of Infection
September 2013
Membrane Proteome: A Funnel-like Viroporin
August 2013
Infectious Diseases: A Pathogen Ubiquitin Ligase
May 2013
Infectious Diseases: A Shared Syringe
May 2013
Infectious Diseases: Determining the Essential Structome
May 2013
Infectious Diseases: Targeting Meningitis
May 2013
NDM-1 and Antibiotics
May 2013
Bacterial Hemophores
January 2013
Microbial Pathogenesis: Computational Epitope Prediction
January 2013
Microbial Pathogenesis: Influenza Inhibitor Screen
January 2013
Microbial Pathogenesis: Measles Virus Attachment
January 2013
Microbial Pathogenesis: NEAT Iron
January 2013
Membrane Proteome: Sphingolipid Synthesis Selectivity
December 2012
A signal sensing switch
September 2012
Gauging needle structure
July 2012
Anthrax Stealth Siderophores
June 2012
A Pseudomonas L-serine dehydrogenase
May 2012
Pilus Assembly Protein TadZ
April 2012
Making Lipopolysaccharide
January 2012
Superbugs and Antibiotic Resistance
December 2011
A change to resistance
November 2011
An effective and cooperative dimer
November 2011
The Perils of Protein Secretion
November 2011
Bacterial Armor
October 2011
Breaking down the defenses
September 2011
Moving some metal
August 2011
Capsid assembly in motion
April 2011
Know thy enemy … structurally
October 2010
Treating sleeping sickness
May 2010
Bacterial spore kinase
April 2010
Hemolysin BL
January 2010
Unusual cell division
October 2009
Anthrax evasion tactics
September 2009
Toxin-antitoxin VapBC-5
September 2009
Antibiotic target
August 2009
July 2009
Tackling influenza
June 2009
You look familiar: the Type VI secretion system
June 2009
Unique SARS
April 2009
Anthrax stealth molecule
March 2009
A new class of bacterial E3 ubiquitination enzymes
January 2009
Antiviral evasion
October 2008
SARS connections
September 2008
SARS Coronavirus Nonstructural Protein 1
June 2008

Research Themes Infectious diseases

Virology: A Bat Influenza Hemagglutinin

SBKB [doi:10.1038/sbkb.2012.188]
Featured Article - March 2014
Short description: The crystal structure of HA antigen from H17N10 bat influenza virus shows how its receptor binding site has diverged from human flu strains.

Overview of the H17 HA trimer (PDB 4I78). Figure courtesy of Ian Wilson.

Influenza virus infection has two surface antigens, hemagglutinin (HA) and neuraminidase (NA). HA initiates viral entry by binding sialic acid moieties of receptors on the cell surface, while NA removes sialic acid from surface glycoproteins and glycolipids of viral progeny to promote their release from the host cell and enhance infectivity. Circulating influenza viruses are classified into subtypes according to the unique combinations of HA and NA proteins they bear, which also determines the range of avian and mammalian species they can infect.

The recent identification of a seventeenth HA subtype from the H17N10 virus that infects bats expanded the known host range of type A influenza viruses and raised the possibility that bats may provide a reservoir of viruses with the potential to prime a human influenza outbreak. To determine whether the H17 HA from A/little yellow-shouldered bat/Guatemala/060/2010 shared the receptor-binding properties of human viral HAs, Wilson (PSI JCSG) and colleagues determined the crystal structure of the recombinant protein at 3.18-Å resolution.

Consistent with its ∼50% sequence conservation with group 1 HAs, H17 forms a trimer with a membrane-distal receptor binding site (RBS) comprised of 190-helix, 130-loop and 220-loop structures characteristic of HAs. However, multiple substitutions of HA residues involved in receptor binding have created an acidic RBS interface that is incompatible with sialic acid binding, including an Asp substitution of Ser/Thr 136 that would interfere with the binding of sialic acid's carboxyl group. Indeed, glycan microarray analysis revealed that H17 has no binding activity for a large panel of sialosides. Moreover, HA proteins undergo large conformational changes at low pH to release a peptide that triggers membrane fusion. Although the fusion peptide sequence is conserved in H17, it appears to be refractory to pH-induced trypsin digestion in vitro, again suggesting that divergent substitutions have caused a loss of low pH-induced membrane fusion function by altering protein properties.

These findings complement previous reports that the N10 NA homolog of H17N10 virus was similarly unable to interact with and cleave sialic acid off host cell receptors to promote viral release. Together, this body of work suggests that, despite the conservation of HA and NA proteins, H17N10 viruses require a distinct membrane receptor for host infection.

Beth Moorefield


  1. X. Zhu et al. Hemagglutinin homologue from H17N10 bat influenza VIRUS exhibits divergent receptor-binding and pH-dependent fusion activities.
    Proc Natl Acad Sci U S A. 110, 1458-63 (2013). doi:10.1073/pnas.1218509110

  2. X. Zhu et al. Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site.
    Proc Natl Acad Sci U S A. 109, 18903-8 (2012). doi:10.1073/pnas.1212579109

  3. Q. Li et al. Structural and functional characterization of neuraminidase-like molecule N10 derived from bat influenza A virus.
    Proc Natl Acad Sci U S A. 109, 18897-902 (2012). doi:10.1073/pnas.1211037109

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health