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Dissecting the roles of individual interactions in protein stability: Lessons from a circularized protein
Author(s) -
Goldenberg David P.
Publication year - 1985
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240290406
Subject(s) - native state , chemistry , hydrogen bond , protein folding , crystallography , trypsin , peptide , biophysics , biochemistry , molecule , biology , enzyme , organic chemistry
A circular form of bovine pancreatic trypsin inhibitor (BPTI) has been prepared by introducing a peptide bond between the N‐ and C‐termini, which are in close proximity in the native conformation. The pathway and energetics of the disulphide‐coupled folding transition of the circular protein have been studied using methods applied previously to the unmodified protein. The cross‐link between the termini was found not to significantly stabilize the native state in spite of the expected reduction in entropy of the unfolded protein. This unexpected result has led to a reexamination of the stabilization expected from a cross‐link, considering effects on the native, as well as unfolded, states of the protein. The greatest stabilization is expected when the cross‐linked groups are held rigidly in the native protein in the optimum orientation for forming the cross‐link. Similar analyses, utilizing thermodynamic cycles, can be applied to other interactions that stabilize native proteins, including disulphide bonds, salt bridges, and hydrogen bonds and to modifications to the protein that remove them. In general, the contribution of an individual interaction to the stability of the native state depends on the extent to which the interaction is favored in the native conformation, which can vary greatly depending on the local environment of the interacting groups.