Development of free-energy-based models for chaperonin containing TCP-1 mediated folding of actin

作者：Altschuler Gabriel M; Willison Keith R^*

来源：Journal of the Royal Society Interface, 2008, 5(29): 1391-1408.

DOI：10.1098/rsif.2008.0185

• actin
• chaperonin-containing TCP-1
• protein folding
• chaperones
• free-energy landscapes

A free-energy-based approach is used to describe the mechanism through which chaperonin-containing TCP-1 (CCT) folds the. lament-forming cytoskeletal protein actin, which is one of its primary substrates. The experimental observations on the actin folding and unfolding pathways are collated and then re-examined from this perspective, allowing us to determine the position of the CCT intervention on the actin free-energy folding landscape. The essential role for CCT in actin folding is to provide a free-energy contribution from its ATP cycle, which drives actin to fold from a stable, trapped intermediate I(3), to a less stable but now productive folding intermediate I(2). We develop two hypothetical mechanisms for actin folding founded upon concepts established for the bacterial type I chaperonin GroEL and extend them to the much more complex CCT system of eukaryotes. A new model is presented in which CCT facilitates free-energy transfer through direct coupling of the nucleotide hydrolysis cycle to the phases of actin substrate maturation.

• 出版日期2008-12-6