Proteins can adopt totally different folded conformations

The three-dimensional structure of a protein is determined by interactions between its amino acids and by interactions of the amino acids with molecul es of the environment. The great influence of the latter interactions is de monstrated for the enzyme phosphoglycerate kinase from yeast (PGK). In the native state, PGK is a compact, bilobal molecule; 35 % and 13 % of its amin o acids are organised in the form of alpha-helices and beta-sheets, respect ively. The molecules unfold at acidic pH and low ionic strength forming ran dom-walk structures with a persistence length of 3 nm. More than 90% of the amino acid residues of the ensemble have phi,psi-angles corresponding to t hose of a straight beta-chain. Upon addition of 50 % (v/v) trifluoroethanol to the acid-unfolded protein, the entire molecule is transformed into a ro d-like, flexible alpha-helix. Addition of anions, such as chloride or trich loroacetate, to the acid-unfolded protein leads to the formation of amyloid -like fibres over a period of many hours when the anion concentration excee ds a critical limit. Half of the amino acid residues are then organised in beta-sheets. Both of the non-natively folded states of PGK contain more reg ular secondary structure than the native one. The misfolding starts in both cases from the acid-unfolded state, in which the molecules are essentially more expanded than in other denatured states, e.g. those effected by tempe rature or guanidine hydrochloride. (C) 1999 Academic Press.