Mechanisms of Macromolecular Machines

 

Characterisation of multi-protein complexes

Using a hybrid approach, we aim to establish fundamental principles underlying the assembly of multi-protein complexes, define their structures, gain insight into their activities and regulation, and identify roles for proteins of unknown function. 


We focus on proteins which play fundamental roles within the cell (e.g. regulation of gene expression) and these are often medically relevant.


One main goal of our work 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 the Ccr4-Not complex. 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.


 

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