Influenza Hemagglutinin

1
Influenza Hemagglutinin

• Jodi Ann Hadden
• BCMB 8010
• University of Georgia

2
Introduction

• Type I integral membrane glycoprotein
• Imbedded in surface of Influenza A virus
• Two roles
• Viral attachment
• Membrane fusion

Figure created from PDB ID 1RVT 11 using VMD
53.
3
Structure

• Homotrimer
• Monomers
• HA0 ? HA1 HA2
• HA1
• Globular head domain
• Jelly rolls of 8 antiparallel b-strands (116
  261)
• HA2
• Transmembrane domain
• 3 fold to form central a-helical coiled coil

Figure created from PDB ID 1RUZ 11 using VMD
53.
4
Binding Site

• Sides
• 190 helix (190 198)
• 130 loop (135 138)
• 220 loop (221 228)
• Base
• Y 98
• W 158
• H 183
• Y 195

Figures created from PDB ID 1RUZ 11 using VMD
53.
5
Binding Site
Figures created from PDB ID 1RUY 11 using VMD
53.
6
Binding Site

• Sides
• 190 helix (190 198)
• 130 loop (135 138)
• 220 loop (221 228)
• Base
• Y 98
• W 158
• H 183
• Y 195

Figures created from PDB ID 1RVT 11 using VMD
53.
7
Binding Site

• Sides
• 190 helix (190 198)
• 130 loop (135 138)
• 220 loop (221 228)
• Base
• Y 98
• W 158
• H 183
• Y 195

Figures created from PDB ID 1RVT 11 using VMD
53.
8
Spring-Loaded Mechanism

• Globular heads dissociate
• Destabilized by low pH
• Loop ? helix (55-75)
• Propels fusion peptide to membrane insertion
• HA tilts on its side
• Juxtaposes membranes and fusion pore forms
• Helix ? loop (105-112)
• Enlarges fusion pore

Figure created from PDB ID 1RUZ 11 using VMD
53.
9
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10
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• Full paper and references at http//jodih.myweb.ug
  a.edu/bcmb8010/InfluenzaHemagglutinin.pdf