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 molecules of the environment. The great influence of the latter interactions is demonstrated for the enzyme phosphoglycerate kinase from yeast (PGK). In the native state, PGK is a compact, bilobal molecule; 35% and 13% of its amino acids are organised in the form of alpha-helices and beta-sheets, respectively. The molecules unfold at acidic pH and low ionic strength forming random-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 those of a straight beta-chain. Upon addition of 50% (v/v) trifluoroethanol to the acid-unfolded protein, the entire molecule is transformed into a rod-like, flexible alpha-helix. Addition of anions, such as chloride or trichloroacetate, to the acid-unfolded protein leads to the formation of amyloid-like fibres over a period of many hours when the anion concentration exceeds 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 regular 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 temperature or guanidine hydrochloride.
Damaschun
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Humboldt-Universität zu Berlin, Institut für Biologie, c/o Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, Berlin, PF 740238, D-13092, Germany. gdamasc@mdc-berlin.de
Damaschun
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H
Gast
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Zirwer
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D000838:Anions; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D010735:Phosphoglycerate Kinase / Q000737:chemistry; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D000838:Anions; D010735:Phosphoglycerate Kinase