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| THE MOLTEN GLOBULE INTERMEDIATE OF APOMYOGLOBIN AND THE PROCESS OF PROTEIN FOLDING |
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| Author(s): BARRICK D, BALDWIN RL |
| Source: PROTEIN SCIENCE Volume: 2 Issue: 6 Pages: 869-876 Published: JUN 1993 |
| Times Cited: 166 References: 36 |
| Abstract: The molten globule model for the beginning of the folding process, which originated with Kuwajima's studies of alpha-lactalbumin (Kuwajima, K., 1989, Proteins Struct. Funct. Genet. 6, 87-103, and references therein), states that. for those proteins that exhibit equilibrium molten globule intermediates, the molten globule is a major kinetic intermediate near the start of the folding pathway. Pulsed hydrogen-deuterium exchange measurements confirm this model for apomyoglobin (Jennings, P.A. & Wright, P.E., in prep.). The energetics of the acid-induced unfolding transition, which have been determined by fitting a minimal three-state model (N double-line arrow pointing left and right I double-line arrow pointing left and right U; N = native. I = molten globule intermediate, U = unfolded) show that I is more stable than U at neutral pH (Barrick, D. & Baldwin, R.L., 1993, Biochemistry 32, in press), which provides an explanation for why I is formed from U at the start of folding. Hydrogen exchange rates measured by two-dimensional NMR for individual peptide NH protons, taken together with the CD spectrum of I, indicate that moderately stable helices are present in I at the locations of the A, G, and H helices of native myoglobin (Hughson, F.M., Wright, P.E., & Baldwin, R.L., 1990, Science 249, 1544-1548). Directed mutagenesis experiments indicate that the interactions between the A, G, and H helices in I are loose (Hughson, F.M., Barrick, D., & Baldwin, R.L., 1991, Biochemistry 30, 4113-4118), which can explain why I is formed rapidly from U at the start of folding. These experiments are consistent with the explanation proposed earlier (Baldwin, R.L., 1989, Trends Biochem. Sci. 14, 291-294) for the stabilization of native secondary structures in molten globule intermediates, namely that each unit of native secondary structure has a hydrophobic face, and the hydrophobic surfaces of two units of secondary structure can interact loosely to provide mutual stabilization. These topics are discussed here in the light of some additional results. |
| Document Type: Editorial Material |
| Language: English |
Addresses:
1. STANFORD UNIV, BECKMAN CTR, DEPT BIOCHEM, STANFORD, CA 94305 USA |
| Publisher: CAMBRIDGE UNIV PRESS, 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: LD535 |
| ISSN: 0961-8368 |
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