Mechanisms of Macromolecular Machines


Characterisation of multi-protein complexes

A main goal of the lab is to understand the molecular mechanisms of addition and removal of mRNA poly(A) tails, performed by Cleavage and Polyadenylation Factor (CPF), Pan2–Pan3 and Ccr4-Not. We also study the Fanconi Anaemia core complex, a large E3 ubiquitin ligase involved in DNA repair, to understand how it monoubiquitinates its substrate proteins (FANCD2-FANCI).

We purify these complexes, reconstitute their biochemical activities and determine their structures to gain mechanistic insights. We use a hybrid approach to establish fundamental principles underlying assembly of multi-protein complexes, define their structures, gain insight into their activities and regulation, and identify roles for proteins of unknown function. 


Lori A. Passmore, MRC Laboratory of Molecular Biology, Cambridge