DIMACS Seminar on Math and CS in Biology

Title:

Experimental Approaches to Protein Structure, Function and Folding

Speaker:

Fred Hughson

Princeton University

Place:

Princeton Computer Science Department

Computer Science Building, Room 402

Princeton University

Time:

1:00 PM

Tuesday, November 28, 1995

Abstract:

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.

References:

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