Conformational rearrangements of an archaeal chaperonin upon ATPase cycling

Chaperonins are double-ring protein assemblies with a central cavity that provides a sequestered environment for in vivo protein folding. Their reaction cycle is thought to consist of a nucleotide-regulated alternation between an open substrate-acceptor state and a closed folding-active state. The cavity of ATP-charged group I chaperonins, typified by Escherichia coil GroEL [1], is sealed off by a co-chaperonin, whereas group II chaperonins - the archaeal thermosome and eukaryotic TRIC/CCT [2] - possess a built in lid [3-5]. The mechanism of the lid's rearrangements requires clarification, as even in the absence of nucleotides, thermosomes of Thermoplama acidophilum appear open in vitrified ice [6] and dosed in crystals [4]. Here we analyze the conformation of the thermosome at each step of the ATPase cycle by small angle neutron scattering. The apo-chaperonin is open in solution, and ATP binding induces Its further expansion. Closure seems to occur during ATP hydrolysis and before phosphate release, and represents the rate limiting step of the cycle. The same closure can be triggered by the crystallization buffer. Thus, the allosteric regulation of group II chaperonins appears different from that of their group I counterparts. (C) 2000 Elsevier Science Ltd. All rights reserved. [References: 21