title: Divergent substrate-binding mechanisms reveal an evolutionary specialization of eukaryotic prefoldin compared to its archaeal counterpart.
abstract: Prefoldin (PFD) is a molecular chaperone that stabilizes and then delivers unfolded proteins to a chaperonin for facilitated folding. The PFD hexamer has undergone an evolutionary change in subunit composition, from two PFDalpha and four PFDbeta subunits in archaea to six different subunits (two alpha-like and four beta-like subunits) in eukaryotes. Here, we show by electron microscopy that PFD from the archaeum Pyrococcus horikoshii (PhPFD) selectively uses an increasing number of subunits to interact with nonnative protein substrates of larger sizes. PhPFD stabilizes unfolded proteins by interacting with the distal regions of the chaperone tentacles, a mechanism different from that of eukaryotic PFD, which encapsulates its substrate inside the cavity. This suggests that although the fundamental functions of archaeal and eukaryal PFD are conserved, their mechanism of substrate interaction have diverged, potentially reflecting a narrower range of substrates stabilized by the eukaryotic PFD.
authors.affiliation: Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Campus de la Universidad Autónoma de Madrid, Darwin 3, 28049 Madrid, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Martín-Benito
authors.forename: Juan
authors.initials: J
authors.lastname: Gómez-Reino
authors.forename: Peter C
authors.initials: PC
authors.lastname: Stirling
authors.forename: Victor F
authors.initials: VF
authors.lastname: Lundin
authors.forename: Paulino
authors.initials: P
authors.lastname: Gómez-Puertas
authors.forename: Jasminka
authors.initials: J
authors.lastname: Boskovic
authors.forename: Pablo
authors.initials: P
authors.lastname: Chacón
authors.forename: José J
authors.initials: JJ
authors.lastname: Fernández
authors.forename: José
authors.initials: J
authors.lastname: Berenguer
authors.forename: Michel R
authors.initials: MR
authors.lastname: Leroux
authors.forename: José M
authors.initials: JM
authors.lastname: Valpuesta
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D005057:Eukaryotic Cells / Q000378:metabolism; D019143:Evolution, Molecular; D008854:Microscopy, Electron; D018832:Molecular Chaperones / Q000737:chemistry* / Q000648:ultrastructure*; D011487:Protein Conformation; D017510:Protein Folding; D021122:Protein Subunits / Q000737:chemistry; D043902:Pyrococcus horikoshii / Q000378:metabolism*
chemical_list: D019843:Archaeal Proteins; D018832:Molecular Chaperones; D021122:Protein Subunits; C112806:prefoldin