The formation of a native-like structure containing eight conserved hydrophobic residues is rate limiting in two-state protein folding of ACBP.
The acyl-coenzyme A-binding proteins (ACBPs) contain 26 highly conserved sequence positions. The majority of these have been mutated in the bovine protein, and their influence on the rate of two-state folding and unfolding has been measured. The results identify eight sequence positions, out of 24 probed, that are critical for fast productive folding. The residues are all hydrophobic and located in the interface between the N- and C-terminal helices. The results suggest that one specific site dominated by conserved hydrophobic residues forms the structure of the productive rate-determining folding step and that a sequential framework model can describe the protein folding reaction.
Kragelund
B B
BB
Carlsberg Laboratorium, Valby, Copenhagen, Denmark.
Osmark
P
P
Neergaard
T B
TB
Schiødt
J
J
Kristiansen
K
K
Knudsen
J
J
Poulsen
F M
FM
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D017124:Conserved Sequence / Q000235:genetics*; D026261:Diazepam Binding Inhibitor; D019791:Guanidine; D006860:Hydrogen Bonding; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D000072236:Methyl-Accepting Chemotaxis Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
D001426:Bacterial Proteins; D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D010455:Peptides; D010940:Plant Proteins; D012097:Repressor Proteins; C093336:chymotrypsin inhibitor 2; D019791:Guanidine