This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Influenza hemagglutinin is a trimeric glycoprotein that mediates the fusion of viral and host membranes following endocytosis. We have conducted solution small-angle x-ray scattering (SAXS) studies of bromelain-released hemagglutinin at the pH of early endosomes. Three-dimensional structural models of BHA at neutral and mildly acidic pH were reconstructed from the SAXS data. A pseudoatomic model was constructed by merging the neutral pH crystal structure and SAXS shape envelope. The model suggests that at the pH of early endosomes, the HA1 globular domains remain associated such that the spike appears mostly intact, however the fusion peptide at the N-terminus of the HA2 subunits as well as significant, associated portions of HA2 appear to have reorganized and may be presented to face the host cell membrane. The model also suggests that a hydrophobic core formed by a portion of the central HA2 helical bundle and possibly an inserted loop from the HA1 subunits helps to maintain the integrity of the spike during fusion activation.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-30
Application #
7954203
Study Section
Special Emphasis Panel (ZRG1-BPC-E (40))
Project Start
2009-03-01
Project End
2010-02-28
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
30
Fiscal Year
2009
Total Cost
$405
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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