Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037
Apomyoglobin has long been used as a paradigmatic system for the study of the protein folding problem. Nevertheless, the native state of apomyoglobin has remained poorly characterized. We have used multi-dimensional heteronuclear NMR spectroscopy to obtain detailed residue specific information about the native state of apomyoglobin (1). In addition, using a similar approach, we are making progress towards sequence-specific NMR resonance assignments for the low pH acid-intermediate "molten globule" state of apomyoglobin. This state has been shown to be populated on the kinetic folding pathway of apomyoglobin (2,3), and any structural insights obtained for this state should prove highly useful in understanding the folding of apomyoglobin. Initial data confirm helicity in regions corresponding to the A, G, and H helices of the native protein, which are anticipated to form a hydrophobic core in the intermediate state. A tantalizing glimpse is also provided into the conformation of other regions of the intermediate state, for which no previous structural information has been available.
1) Eliezer, D., & Wright, P. E. (1996) J. Mol. Biol. in press.
2) Jennings, P. A., & Wright, P. E. (1993) Science. 262:892-896.
3) Eliezer, D., Jennings, P. A., Wright, P. E., Doniach, S., Hodgson, K.
O., & Tsuruta, H. (1995) Science. 270:487-488.