Structure of the Molecular Chaperone Prefoldin

Abstract

Prefoldin (GimC) is a hexameric molecular chaperone The archaeal Group II chaperonin (thermosome) is complex built from two related classes of subunits closely related to its eukaryotic homologue TRiC and present in all eukaryotes and archaea. Prefoldin (Gutsche et al., 1999). In contrast, Hsp70 proteins and interacts with nascent polypeptide chains and, in vitro, TF are generally missing from the archaeal kingdom can functionally substitute for the Hsp70 chaperone though some archaea have acquired Hsp70, presumably system in stabilizing non-native proteins for subseby lateral gene transfer (Gribaldo et al., 1999). However, quent folding in the central cavity of a chaperonin. all archaea contain a homologue of the recently de-Here, we present the crystal structure and characterscribed eukaryotic molecular chaperone prefoldin/GimC ization of the prefoldin hexamer from the archaeum (Geissler et al., 1998; Vainberg et al., 1998; Hansen et al., Methanobacterium thermoautotrophicum. Prefoldin 1999; Siegers et al., 1999), which is absent in bacteria. has the appearance of a jellyfish: its body consists of Archaeal prefoldin has been shown to have ATP-indea double ␤ barrel assembly with six long tentacle-like pendent chaperone properties similar to that of Hsp70 coiled coils protruding from it. The distal regions of in a folding pathway with a chaperonin in vitro (Leroux the coiled coils expose hydrophobic patches and are et al., 1999), and may perform Hsp70-like functions required for multivalent binding of nonnative proteins. in vivo. The structures and functions of Hsp70 and chaper-* To whom correspondence should be addressed (email: ismail@ tensions of their apical domains that are thought to memoarefi.com [I. M.],

Predicted highly expressed genes in archaeal genomes

“…The crenarchaea do not contain the ␣ subunit ( Table 2). Pfd is considered to perform HSP70-like functions (41), albeit the sequences and structures of these proteins are substantially different.…”

“…PapD͞FimC are other chaperones͞periplasmic, and disulfide oxidase proteins cytoplasmic chaperones. Tig exhibits PPI activity in vitro and contains a PPI motif of the cyclophilin family in most bacteria, binds at the ribosome polypeptide tunnel exit, and cooperates with DnaK during de novo protein folding (39)(40)(41)(42). In this respect, NAC substitutes for Tig in eukaryotes and possibly in archaea (38).…”

“…Prefoldin generally has six distinct subunit types in eukaryotes, at most two subunit types (␣ and ␤) in archaea (Table 2), and is absent from bacteria (22). Prefoldin may assist de novo protein folding when interacting with CCT (41). HSP90 (HtpG) is widely distributed in Bacteria but is absent from Archaea and also from the genomes of the deeply branching bacterial species Aquifex aeolicus and Thermotoga maritima (22).…”

“…These include operon gene organization, the SD motif that provides control on mRNA translation initiation, and the presence of several clusters of RP. The most pronounced PHX genes are the thermosome chaperones (distant homologs of GroEL) and the chaperone prefoldin, which is hypothesized to substitute for the activities of Trigger factor and HSP70 (22,38,41). Based on the Clusters of Orthologous Groups database (www.ncbi.nlm.nih.gov͞COG, 2004), all bacterial and archaeal genomes share only 67 genes of which 30 are ribosomal protein genes, 14 are amino acetyl-tRNA synthetases, and several are major protein synthesis and processing factors.…”

New insights into the biogenesis of nuclear RNA polymerases?This paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.

“…2 for a schematic representation of the prefoldin-like module components). Once assembled, the β hairpins form the core of the complex, two 8-stranded β barrels, while the coiled-coil helixes resemble tentacle-like appendages that first mediate substrate binding (Siegert et al 2000;Lundin et al 2004). The PFD complex binds unfolded, newly synthesized poly-peptides and delivers them to the CCT chaperone for proper folding.…”