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^1–3 Tubulin is a major cytosolic protein whose assembly into microtubules is critical to many cellular processes^4–8. Although numerous studies have focused on the expression of tubulin^9–20, little is known about the processes whereby newly translated tubulin subunits acquire conformations that enable them to form α-β-heterodimers. We examined the biogenesis of α- and β-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.