Abstract by William Ludlam

Personal Infomation

Presenter's Name

William Ludlam



Degree Level



Jorge Cuellar
Takuma Aoba
Madhura Dhavale
Nicole Tensmeyer
Aman Makaju
Sarah Franklin
Barry Willardson
Jose Valpuest

Abstract Infomation


Chemistry and Biochemistry

Faculty Advisor

Barry Willardson


Structure of the mLST8-CCT Folding Intermediate


The mechanistic target of rapamycin (mTOR) kinase is a master regulator of eukaryotic cell metabolism, growth and survival.  mTOR functions in two distinct complexes, called mTORC1 and mTORC2. While mTORC functions have been studied extensively, little is known about how the individual subunits of these complexes are assembled from their nascent polypeptide chains. Here, we provide evidence that an important chaperone for cytosolic proteins, the chaperonin containing TCP-1 (CCT), is involved in the folding and assembly of the protein mLST8 (mammalian lethal with SEC13 protein 8), a key component of both mTOR complexes.  We have isolated an mLST8 folding intermediate bound to CCT and determined the structure of this complex to 4.4 angstrom resolution by single particle cryo-electron microscopy. This structure represents the highest resolution of a folding substrate inside the CCT cavity to date and shows mLST8 in an unexpected position between the two CCT octamer rings in a near-native conformation.