Structure of eukaryotic prefoldin and of its complexes with unfolded actin and the cytosolic chaperonin CCT.
The biogenesis of the cytoskeletal proteins actin and tubulin involves interaction of nascent chains of each of the two proteins with the oligomeric protein prefoldin (PFD) and their subsequent transfer to the cytosolic chaperonin CCT (chaperonin containing TCP-1). Here we show by electron microscopy that eukaryotic PFD, which has a similar structure to its archaeal counterpart, interacts with unfolded actin along the tips of its projecting arms. In its PFD-bound state, actin seems to acquire a conformation similar to that adopted when it is bound to CCT. Three-dimensional reconstruction of the CCT:PFD complex based on cryoelectron microscopy reveals that PFD binds to each of the CCT rings in a unique conformation through two specific CCT subunits that are placed in a 1,4 arrangement. This defines the phasing of the CCT rings and suggests a handoff mechanism for PFD.
Martín-Benito
Jaime
J
Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Boskovic
Jasminka
J
Gómez-Puertas
Paulino
P
Carrascosa
José L
JL
Simons
C Torrey
CT
Lewis
Sally A
SA
Bartolini
Francesca
F
Cowan
Nicholas J
NJ
Valpuesta
José M
JM
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000378:metabolism*; D008297:Male; D017014:Methanobacterium / Q000737:chemistry; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D017510:Protein Folding
D000199:Actins; D018832:Molecular Chaperones; C112806:prefoldin; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins