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1hgf
From Proteopedia
| 1hgf, resolution 3.00Å () | |||||||||
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| Sites: | , , , , , , , , , , , , , , , , , , , and | ||||||||
| Ligands: | , | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
How Influenza Escapes Vaccines
Influenza hemagglutinin, the structure of which is shown here, is a glycoprotein on the surface of influenza virus particles that enables them to attach to and infect host cells. Antibodies that bind to hemagglutinin are a major defense mechanism that prevent infection. The RNA genome of influenza is characterized by a high mutation rate. Mutations on the surface of hemagglutinin tend to be protective for the virus. They tend to be retained because they tend to reduce the binding strength, and hence the host defensive capability, of antibodies that recognize the un-mutated hemagglutinin[1]. Influenza vaccines include hemagglutinins and they induce anti-hemagglutinin antibodies in vaccinated individuals. Often, however, by the time the vaccines can be designed, produced, and disseminated, mutant influenza viruses have arisen that can cause disease in vaccinated individuals[2].
If you show the Evolutionary Conservation of the structure on this page (using the blue bars below the molecule), you will see highly variable surface amino acids. These represent sites of mutations that have been retained in wild strains of influenza because they improve virus survival[1].
BINDING OF INFLUENZA VIRUS HEMAGGLUTININ TO ANALOGS OF ITS CELL-SURFACE RECEPTOR, SIALIC ACID: ANALYSIS BY PROTON NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY AND X-RAY CRYSTALLOGRAPHY
The interaction between influenza virus hemagglutinin and its cell-surface receptor, 5-N-acetylneuraminic acid (sialic acid), was probed by the synthesis of 12 sialic acid analogs, including derivatives at the 2-carboxylate, 5-acetamido, 4-, 7-, and 9-hydroxyl, and glycosidic positions. The equilibrium dissociation constants of these analogs were determined by nuclear magnetic resonance spectroscopy. Ligand modifications that reduced or abolished binding included the replacement of the 2-carboxylate with a carboxamide, the substitution of azido or N-benzyloxycarbonyl groups for the 5-acetamido group, and the replacement of the 9-hydroxyl with amino or O-acetyl moieties. Modifications having little effect on binding included the introduction of longer chains at the 4-hydroxyl position, the replacement of the acetamido methyl group with an ethyl group, and the removal of the 7-hydroxyl group. X-ray diffraction studies yielded 3 A resolution crystal structures of hemagglutinin in complex with four of the synthetic analogs [alpha-2-O-methyl-, 4-O-acetyl-alpha-2-O-methyl-, 9-amino-9-deoxy-alpha-2-O-methyl-, and alpha-2-O-(4'-benzylamidocarboxybutyl)-N-acetylneuraminic acid] and with the naturally occurring cell-surface saccharide (alpha 2-3)sialyllactose. The X-ray studies unambiguously establish the position and orientation of bound sialic acid, indicate the position of the lactose group of (alpha 2-3)sialyllactose, and suggest the location of an alpha-glycosidic chain (4'-benzylamidocarboxybutyl) that increases the binding affinity of sialic acid by a factor of about 3. Although the protein complexed with alpha-2-O-methylsialic acid contains the mutation Gly-135-->Arg near the ligand binding site, the mutation apparently does not affect the ligand's position. The X-ray studies allow us to interpret the binding affinities in terms of the crystallographic structure. The results suggest further experiments which could lead to the design of tight binding inhibitors of possible therapeutic value.
Binding of influenza virus hemagglutinin to analogs of its cell-surface receptor, sialic acid: analysis by proton nuclear magnetic resonance spectroscopy and X-ray crystallography., Sauter NK, Hanson JE, Glick GD, Brown JH, Crowther RL, Park SJ, Skehel JJ, Wiley DC, Biochemistry. 1992 Oct 13;31(40):9609-21. PMID:1327122
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1HGF is a 6 chains structure of sequences from Unidentified influenza virus. Full crystallographic information is available from OCA.
Reference
- Sauter NK, Hanson JE, Glick GD, Brown JH, Crowther RL, Park SJ, Skehel JJ, Wiley DC. Binding of influenza virus hemagglutinin to analogs of its cell-surface receptor, sialic acid: analysis by proton nuclear magnetic resonance spectroscopy and X-ray crystallography. Biochemistry. 1992 Oct 13;31(40):9609-21. PMID:1327122
See Also
- Avian Influenza Neuraminidase, Tamiflu and Relenza
- A tutorial on influenza hemagglutinin structure in the Online Macromolecular Museum.
Notes and Literature Cited
- ↑ 1.0 1.1 Knossow M, Skehel JJ. Variation and infectivity neutralization in influenza. Immunology. 2006 Sep;119(1):1-7. PMID:16925526 doi:10.1111/j.1365-2567.2006.02421.x
- ↑ See Influenza in Wikipedia.
Page seeded by OCA on Wed Feb 18 07:40:45 2009
