recent folding results

[kasson]

We are pleased to announce the publication of some of our recent folding results. Per Larsson in my lab is the lead author on this publication, and it details how influenza proteins interact with membranes (and change shape i.e. refold in the membranes). We also look at how some important mutations change this interaction and what this might tell us about critical influenza protein function.

This work involved a series of F@H projects, notably those in the 6050-6099 range and in the 71XX range. We are also continuing this investigation and hope to have more results in the future.

Thanks for your support of Folding@Home!

Article freely available at: http://www.ploscompbiol.org/article/inf ... bi.1002950

Summary reproduced from the article:
Membrane fusion is a common process critical to both cellular function and infection by enveloped viruses. Influenza is a particularly useful model system for studying fusion because the fusion reaction is accomplished by a single protein, hemagglutinin. Furthermore, mutations to the membrane-inserted portion of hemagglutinin have been identified that do not detectably alter the rest of the protein but can either arrest fusion halfway or block it entirely. For influenza at least, it seems that the membrane-inserted hemagglutinin peptide plays a critical role in promoting fusion, perhaps by increasing the local disorder of lipid bilayers. However, we lack a mechanistic understanding sufficient to predict the activity of fusion peptide mutants from their sequence. Here, we have used lipid tail protrusion as a way to measure how much fusion peptides disorder their surrounding bilayer; we see a strong relationship between lipid tail protrusion and the ability of fusion peptide mutants to promote lipid mixing between membranes. Our simulations also predict that this lipid tail protrusion is much more common when the peptides adopt a kinked helix structure than when they are straight or hairpin-like. We therefore hypothesize that, while all three types of structure likely undergo conformational exchange, the kinked helix structure is most active in promoting fusion.