Mechanisms of Macromolecular Machines


Characterisation of multi-protein complexes

Many structural studies have been performed on individual proteins or isolated domains.  However, most proteins form a network of interactions with other proteins and many are components of large complexes in vivo. Our understanding of how proteins assemble to form such complexes and how these complexes function remains limited. 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.

The 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. An understanding of the structures and functions of both CPF and Ccr4-Not will provide fundamental biological insights into this exciting field.

We also study the Fanconi Anaemia core complex, a large E3 ubiquitin ligase involved in DNA repair.


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