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Solution structure of a peptide model of a region important for the folding of α‐lactalbumin provides evidence for the formation of nonnative structure in the denatured state
Author(s) -
Demarest Stephen J.,
Raleigh Daniel P.
Publication year - 2000
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(20000201)38:2<189::aid-prot7>3.0.co;2-f
Subject(s) - native state , chemistry , folding (dsp implementation) , random coil , protein folding , phi value analysis , population , conformational isomerism , protein structure , crystallography , lactalbumin , alpha lactalbumin , protein secondary structure , molten globule , folding funnel , circular dichroism , downhill folding , molecule , biochemistry , organic chemistry , demography , sociology , electrical engineering , engineering
Elucidating the properties of the denatured state of proteins under conditions relevant for their folding is a key factor in understanding the folding process. We show that a peptide corresponding to residues 111–120 of human α‐lactalbumin has a pronounced propensity to adopt nonnative structure in aqueous solution. Two‐dimensional NMR provides evidence for a structured, nonnative conformation in fast exchange with a random coil ensemble. A total of 78 Rotating Frame Overhauser Effects (ROEs) were used to calculate the conformation of the structured population. A nonnative cluster of hydrophobic residues involving the side chains of K114, W118, L119, and A120 is observed, which helps to stabilize a turnlike conformation in the vicinity of residues 115–118. The structure in 30% (vol/vol) TFE was also calculated. Interestingly, the addition of TFE did not simply amplify the population of the structured conformer observed in H 2 O, but instead induced a new conformation. The implications for the folding of the intact protein are discussed. We also discuss the implications of this study for the relevance of the use of mixed TFE/H 2 O solvent systems to study isolated peptides. Proteins 2000;38:189–196. © 2000 Wiley‐Liss, Inc.