Multiple Subsets of Side-Chain Packing in Partially Folded States of α-Lactalbumins

Photochemically induced dynamic nuclear polarization NMR pulse-labeling techniques have been used to obtain detailed information about side-chain surface accessibilities in the partially folded (molten globule) states of bovine and human α-lactalbumin prepared under a variety of well defined conditi...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 102; no. 25; pp. 8899 - 8904
Main Authors Mok, K. Hun, Nagashima, Toshio, Day, Iain J., Hore, P. J., Dobson, Christopher M., Frieden, Carl
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 21.06.2005
National Acad Sciences
Subjects
Amino Acid Sequence
Animals
Biochemistry
Biological Sciences
Biophysics
Cattle
Chemical equilibrium
Humans
Indoles
Lactalbumin - chemistry
Lactalbumin - metabolism
Lasers
Magnetic Resonance Spectroscopy - methods
Models, Molecular
Molecules
NMR
Nuclear magnetic resonance
Protein Conformation
Protein Folding
Protein refolding
Proteins
Protons
Solvents
Topology
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Summary:Photochemically induced dynamic nuclear polarization NMR pulse-labeling techniques have been used to obtain detailed information about side-chain surface accessibilities in the partially folded (molten globule) states of bovine and human α-lactalbumin prepared under a variety of well defined conditions. Pulse labeling involves generating nuclear polarization in the partially folded state, rapidly refolding the protein within the NMR sample tube, then detecting the polarization in the well dispersed native-state spectrum. Differences in the solvent accessibility of specific side chains in the various molten globule states indicate that the hydrophobic clusters involved in stabilizing the α-lactalbumin fold can be formed from interactions between a variety of different hydrophobic residues in both native and nonnative environments. The multiple subsets of hydrophobic clusters are likely to result from the existence of distinct but closely related local minima on the free-energy landscape of the protein and show that the fold and topology of a given protein may be formed from degenerate groups of side chains.
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To whom correspondence may be addressed. E-mail: cmd44@cam.ac.uk or peter.hore@chemistry.oxford.ac.uk.
Present address: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605.
Author contributions: K.H.M., T.N., I.J.D., P.J.H., and C.M.D. designed research; K.H.M., T.N., and I.J.D. performed research; K.H.M., T.N., I.J.D., P.J.H., and C.M.D. contributed new reagents/analytic tools; K.H.M., T.N., I.J.D., P.J.H., and C.M.D. analyzed data; and K.H.M., P.J.H., and C.M.D. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Present address: Protein Research Group, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
Edited by Carl Frieden, Washington University School of Medicine, St. Louis, MO, and approved April 14, 2005
Abbreviations: CIDNP, chemically induced dynamic nuclear polarization; MG, molten globule; N state, native state; A state, acidic MG state; HLA, human α-lactalbumin; BLA, bovine α-lactalbumin; P, partly denatured.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0500661102