Biological function in a non-native partially folded state of a protein.
As structural flexibility is known to be required for enzyme catalysis and pattern recognition and a significant fraction of eukaryotic proteins appear to be unfolded or contain unstructured regions, biological activity of conformational states distinct from fully folded structures could be more common than previously thought. By applying a procedure that allows the recovery of enzymatic activity to be monitored in real time, we show that a non-native state populated transiently during folding of the acylphosphatase from Sulfolobus solfataricus is enzymatically active. The structural characterization of this partially folded state reveals that enzymatic activity is possible even if the catalytic site is structurally heterogeneous, whereas the remainder of the structure acts as a scaffold. These results extend the spectrum of biological functions carried out in the absence of a folded state to include enzyme catalysis.
Bemporad
Francesco
F
Dipartimento di Scienze Biochimiche, Università degli Studi di Firenze, Firenze, Italy.
Gsponer
Joerg
J
Hopearuoho
Harri I
HI
Plakoutsi
Georgia
G
Stati
Gianmarco
G
Stefani
Massimo
M
Taddei
Niccolò
N
Vendruscolo
Michele
M
Chiti
Fabrizio
F
D017766:Acid Anhydride Hydrolases / Q000737:chemistry* / Q000235:genetics; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics; D002384:Catalysis; D020134:Catalytic Domain; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D048229:Sulfolobus solfataricus / Q000201:enzymology*; D013816:Thermodynamics; D000097024:Acylphosphatase
D017766:Acid Anhydride Hydrolases; D019843:Archaeal Proteins; D000097024:Acylphosphatase