title: TCP1 complex is a molecular chaperone in tubulin biogenesis.
abstract: A role in folding of newly translated proteins in the cytosol of eukaryotes has been proposed for t-complex polypeptide-1 (TCP1), although its molecular targets have not yet been identified. Tubulin is a major cytosolic protein whose assembly into microtubules is critical to many cellular processes. Although numerous studies have focused on the expression of tubulin, little is known about the processes whereby newly translated tubulin subunits acquire conformations that enable them to form alpha-beta-heterodimers. We examined the biogenesis of alpha- and beta-tubulin in rabbit reticulocyte lysate, and report here that newly translated tubulin subunits entered a 900K complex in a protease-sensitive conformation. Addition of Mg-ATP, but not nonhydrolysable analogues, released the tubulin subunits as assembly-competent protein with a conformation that was relatively protease-resistant. The 900K complex purified from reticulocyte lysate contained as its major constituent a 58K protein that cross-reacted with a monoclonal antiserum against mouse TCP1. We conclude that TCP1 functions as a cytosolic chaperone in the biogenesis of tubulin.
authors.affiliation: Department of Pharmacology, Case Western Reserve School of Medicine, Cleveland, Ohio 44106.
authors.forename: M B
authors.initials: MB
authors.lastname: Yaffe
authors.forename: G W
authors.initials: GW
authors.lastname: Farr
authors.forename: D
authors.initials: D
authors.lastname: Miklos
authors.forename: A L
authors.initials: AL
authors.lastname: Horwich
authors.forename: M L
authors.initials: ML
authors.lastname: Sternlicht
authors.forename: H
authors.initials: H
authors.lastname: Sternlicht
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D056427:t-Complex Genome Region
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014404:Tubulin; D000255:Adenosine Triphosphate; D003513:Cycloheximide; C116196:PPP1R11 protein, human; D044767:Ubiquitin-Protein Ligases