DIMACS Seminar on Math and CS in Biology


Experimental Approaches to Protein Structure, Function and Folding


Fred Hughson
Princeton University


Princeton Computer Science Department
Computer Science Building, Room 402
Princeton University


1:00 PM
Tuesday, November 28, 1995


One goal of experimental studies of protein folding is to understand how the amino acid sequence of a protein determines its three-dimensional structure. For most proteins, only two states have been observed: native and fully unfolded. The protein apomyoglobin is useful for folding studies because a partly-folded form is stable under appropriate conditions and can be characterized structurally. Such characterization identifies a subdomain of the protein structure that is independently stable. Site-directed mutagenesis shows that this independently-folded subdomain has some properties of a molten globule. This work represents a first step toward dissecting the hierarchy of interactions which stabilize native proteins.

I will also discuss hemagglutinin, the protein which influenza virus uses to gain entry into cells. This protein becomes active via a conformational change of unprecedented magnitude. Its structure has been determined by X-ray crystallography in both conformations. These results and others lead to proposals regarding the energetic basis for the conformational change. They also hint at a mechanism for virus entry into cells.


1. Hughson, F.M., Wright, P.E., and Baldwin, R.L. (1990) Structural characterization of a partly folded apomyoglobin intermediate. Science 249, 1544-1548.

2. Bullough, P.A., Hughson, F.M., Skehel, J.J., and Wiley, D.C. (1994) Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 371, 37-43.

Document last modified on November 22, 1995