Projects and Grants per year
Grants and Contracts Details
Description
This award provides support under the Research Supplements to Promote Diveristy in Health]Related
Research Program for Student, Brent Hackett beginning 7/1/12. This supplement is affiliated with the
existing awarded grant using the original abstract below
ABSTRACT:
Membrane fusion, a process critical for viral entry, is promoted by the paramyxovirus fusion (F) proteins.
All F proteins contain a number of common features that play fundamental roles in fusion. However,
significant variations exist between F proteins related to protein activation and promotion of membrane
fusion, and many critical questions remain concerning the mechanism by which fusion is promoted by
these important viral proteins. The long]term objective of our research is to understand the precise
mechanism(s) of paramyxovirus F protein]promoted membrane fusion. Our overall hypothesis is that
the function of domains critical for fusion promotion will be conserved in diverse F proteins, but that
interactions in these domains will modulate triggering mechanisms. To address this important
hypothesis we will pursue the following specific aims: 1.) We will build on our exciting preliminary data
which demonstrates trimer formation of isolated Hendra F transmembrane (TM) domains to define the
role of TM]TM interactions in glycoprotein folding and fusion. We will therefore delineate the residues
critical for TM]TM interactions, and evaluate the role of this interaction in Hendra F folding, trafficking
and fusion; analyze the effect of HRB or cytoplasmic]tail additions on stability of TM]TM interactions;
compare TM]TM interactions for the PIV5 and HMPV F proteins to those observed for the Hendra F TM;
and determine if TM domains from paramyxovirus attachment proteins interact with themselves or with
the F protein TM domains; 2.) We will define the role of low pH and endocytosis in HMPV viral entry and
delineate the role of electrostatic repulsion in the HRB linker region in HMPV F low pH]induced
conformational changes and entry of recombinant viruses and; 3.) We will analyze the role of stabilizing
interactions between HRA and a conserved region of F2, which our studies of PIV5 F indicate can playa
role in triggering, by defining key interactions in this domain in PIV5 F, assessing the stage of fusion
which is affected, analyzing the effect of mutations in this region on viral entry, and analyzing the effect
of mutations to this region in other F proteins. Accomplishing these goals will provide crucial
information on the regions that control the molecular events involved in
Status | Finished |
---|---|
Effective start/end date | 5/15/02 → 1/31/14 |
Funding
- National Institute of Allergy and Infectious Diseases
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Projects
- 1 Finished
-
Paramyxovirus F protein mediated membrane fusion
Dutch, R. (PI), Creamer, T. (CoI) & Fried, M. (CoI)
National Institute of Allergy and Infectious Diseases
5/15/02 → 8/14/14
Project: Research project