Student Hosted Colloquium

Thursday, March 22nd
Professor Lukas Tamm
"A Structure-Based model of Viral Cell Entry by Membrane Fusion"

4:15pm - 5:15pm
Braun Auditorium
S.G.Mudd Chemistry Building
Stanford University




This seminar is free and open to the public. All Stanford University Chemistry students are encouraged to attend this special event.

About the Seminar:
Viral membrane fusion is mediated by viral envelope glycoproteins that undergo large conformational changes upon membrane binding and triggering of fusion. As part of this conformational change, a quite hydrophobic and between strains of the same virus highly conserved domain, the “fusion peptide”, is exposed and inserted into the lipid bilayer of the target membrane. Many viral fusion domains form amphipathic structures and insert at oblique angles into lipid bilayers. Using the example of the fusion peptide of influenza virus hemagglutinin, we show that a kinked “boomerang” structure is critical to promote membrane fusion. Mutants that show linear amphipathic structures or more flexibly kinked structures in membranes are unable to mediate fusion in the context of full-length influenza hemagglutinin. A boomerang-shaped fusion domain with a N-terminal serine instead of a glycine proceeds to a hemi-fusion intermediate, but is unable to open a full fusion pore in cell fusion assays. Binding of the fusion peptides to membranes is promoted by enthalpy and opposed by entropy and, therefore, is driven by a “non-classical” hydrophobic effect. Active fusion peptides have higher enthalpies and free energies of binding to lipid bilayers and organize lipids in a different fashion than inactive fusion peptides. These results lead to the “spring-loaded boomerang model” of membrane fusion, in which the fusion domains exert force on the membranes to facilitate the formation of a fusion intermediate that may feature a highly dynamic lipid stalk intermediate before a fusion pore is opened by interaction between the fusion and transmembrane domains of the viral fusion protein. Recent results on the structure and membrane interactions of the HIV gp41 fusion domain suggest that this general mechanism may be conserved between different viruses.
For further reading:
Lai, A.L., Li, Y., and Tamm, L.K. Interplay of proteins and lipids in virus entry by membrane fusion. In: Protein-Lipid Interactions: From Membrane Domains to Cellular Networks, Tamm, L.K., Ed., Wiley-VCH, 2005. pp. 279-303.

AboutTamm:
Lukas K. Tamm received his Ph.D., from the University of Basel in Switzerland. He is currently at the University of Virginia as a Professor with Molecular Physiology and Biological Physics. His research interests are Biomembrane Structure and Function; Membrane Fusion in Viral Cell Entry and Exocytosis; in addition to Lipid-Protein Interactions.

Questions
Please contact Patricia Dwyer at 650-723-4770.