Curr. Biol

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

Dermal Real‐Time Quaking‐Induced Conversion Is a Sensitive Marker to Confirm Isolated Rapid Eye Movement Sleep Behavior Disorder as an Early α‐Synucleinopathy

ABSTRACT:Background:Skin biopsy is apotential tool for the premortem confirmation of anα-synucleinopathy.Objective:The aim was to assess the aggregationassay real-time quaking-induced conversion (RT-QuIC)of skin biopsy lysates to confirm isolated rapid eyemovement sleep behavior disorder (iRBD) as anα-synucleinopathy.Methods:Skin biopsies of patients with iRBD,Parkinson’s disease (PD), and controls were analyzedusing RT-QuIC and immunohistochemical detection ofphospho-α-synuclein.Results:α-Synuclein aggregation was detected in97.4% of iRBD patients (78.4% of iRBD biopsies),87.2% of PD patients (70% of PD biopsies), and 13%of controls (7.9% of control biopsies), with a higherseeding activity in iRBD compared to PD. RT-QuICwas more sensitive but less specific thanimmunohistochemistry.Conclusions:Dermal RT-QuIC is a sensitive methodto detectα-synuclein aggregation in iRBD, and highseeding activity may indicate a strong involvement ofdermal nervefibers in these patients. © 2023 TheAuthors.Movement Disorderspublished by WileyPeriodicals LLC on behalf of International Parkinsonand Movement Disorder Society.Key Words:rapid eye movement sleep behavior dis-order;α-synuclein; Parkinson’s disease; real-timequaking-induced conversion; skin biops