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Title: Characterization of a partly folded protein by NMR methods: Studies on the molten globule state of guinea pig. alpha. -lactalbumin

Journal Article · · Biochemistry; (USA)
DOI:https://doi.org/10.1021/bi00427a002· OSTI ID:5472867

NMR spectroscopy has been used to investigate the structure of a partially folded state of a protein, the molten globule or A-state of {alpha}-lactalbumin. The {sup 1}H NMR spectrum of this species differs substantially from those of both the native and fully unfolded states, reflecting the intermediate level of order. The resolution in the spectrum is limited by the widespread overlap and substantial line widths of many of the resonances. Methods have therefore been developed that exploit the well-resolved spectrum of the native protein to probe indirectly the A-state. A number of resonances of the A-state have been found to be substantially shifted from their positions in the spectrum of the unfolded state and have been identified through magnetization transfer with the native state, under conditions where the two states are interconverting. The most strongly perturbed residues in the A-state were found to be among those that form a hydrophobic core to the native structure. A number of amides were found to be highly protected from solvent exchange in the A-state. These have been identified through pH-jump experiments, which label them in the spectrum of the native protein. They were found to occur mainly in segments that are helical in the native structure. These results enable a model of the A-state to be proposed in which significant conformational freedom exists but where specific elements of native-like structure are preserved.

OSTI ID:
5472867
Journal Information:
Biochemistry; (USA), Vol. 28:1; ISSN 0006-2960
Country of Publication:
United States
Language:
English