Divergent substrate-binding mechanisms reveal an evolutionary specialization of eukaryotic prefoldin compared to its archaeal counterpart.
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.
Martín-Benito
Jaime
J
Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Campus de la Universidad Autónoma de Madrid, Darwin 3, 28049 Madrid, Spain.
Gómez-Reino
Juan
J
Stirling
Peter C
PC
Lundin
Victor F
VF
Gómez-Puertas
Paulino
P
Boskovic
Jasminka
J
Chacón
Pablo
P
Fernández
José J
JJ
Berenguer
José
J
Leroux
Michel R
MR
Valpuesta
José M
JM
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*
D019843:Archaeal Proteins; D018832:Molecular Chaperones; D021122:Protein Subunits; C112806:prefoldin