Accelerated folding in the weak hydrophobic environment of a chaperonin cavity: creation of an alternate fast folding pathway.
Recent experiments suggest that the folding of certain proteins can take place entirely within a chaperonin-like cavity. These substrate proteins experience folding rate enhancements without undergoing multiple rounds of ATP-induced binding and release from the chaperonin. Rather, they undergo only a single binding event, followed by sequestration into the chaperonin cage. The present work uses molecular dynamics simulations to investigate the folding of a highly frustrated protein within this chaperonin cavity. The chaperonin interior is modeled by a sphere with a lining of tunable degree of hydrophobicity. We demonstrate that a moderately hydrophobic environment, similar to the interior of the GroEL cavity upon complexion with ATP and GroES, is sufficient to accelerate the folding of a frustrated protein by more than an order of magnitude. Our simulations support a mechanism by which the moderately hydrophobic chaperonin environment provides an alternate pathway to the native state through a transiently bound intermediate state.
Jewett
A I
AI
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA.
Baumketner
A
A
Shea
J-E
JE
D018833:Chaperonins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D017510:Protein Folding; D013269:Stochastic Processes; D013816:Thermodynamics
D018833:Chaperonins