Professor Laurence Pearl FRS FMedSci
Professor of Structural Biology
University of Sussex
Elected Fellow 2007
structural biology, protein biochemistry, multiprotein complexes, X-ray crystallography, cryoEM, molecular biology
Laurence Pearl is Professor of Protein Crystallography at the Institute of Cancer Research and is a structural biologist of international standing. He has made significant contributions to understanding the structural mechanisms of systems involved in DNA repair, signal transduction, and chaperone-dependent protein activation in cells. His early studies of the structure and mechanism of aspartic and retroviral proteases were seminal in the recognition of HIV protease as a dimeric aspartic protease that could be readily exploited as a therapeutic target in AIDS. He is internationally preeminent in studies of the Hsp90 molecular chaperone, having demonstrated the functional dependence of Hsp90 on ATP, defined the structural mechanism of the ATPase-coupled chaperone cycle, and revealed its complex regulation by co-chaperones such as Cdc37, Aha1 and p23 both structurally and biochemically. In recent work has revealed the structure of the chaperone-coupled E3 ligase CHIP, and has provided the first structural view of an Hsp90 complex with a protein kinase client, Cdk4. These studies have been translated successfully into the development of novel anti-tumour agents that function by disrupting Hsp90-dependent activation of oncogenic proteins.