Author(s): Ma J, Sigler PB, Xu Z, Karplus M
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Abstract GroEL-assisted protein folding is regulated by a cycle of large coordinated domain movements in the 14-subunit double-ring assembly. The transition path between the closed (unliganded) and the open (liganded) states, calculated with a targeted molecular dynamics simulation, shows the highly complex subunit displacements required for the allosteric transition. The early downward motion of the small intermediate domain induced by nucleotide binding emerges as the trigger for the larger movements of the apical and equatorial domains. The combined twisting and upward displacement of the apical domain determined for a single subunit is accommodated easily in the heptamer ring only if its opening is concerted. This is a major source of cooperative ligand binding within a ring. It suggests also that GroEL has evolved so that the motion required for heptamer cooperativity is encoded in the individual subunits. A calculated model for a di-cis 14-subunit assembly is found to be destabilized by strong steric repulsion between the equatorial domains of the two rings, the source of negative cooperativity. The simulation results, which indicate that transient interactions along the transition path are essential for GroEL function, provide a detailed structural description of the motions that are involved in the GroEL allosteric cycle. Copyright 2000 Academic Press.
This article was published in J Mol Biol
and referenced in Journal of Physical Chemistry & Biophysics