Novel β-Propeller of the BTB-Kelch Protein Krp1 Provides a Binding Site for Lasp-1 That Is Necessary for Pseudopodial Extension

Current position: Principal scientific officer, Beatson Institute for Cancer Research, Glasgow, United Kingdom

Education: Ph.D. in 2001 from the University of Glasgow on the molecular biology and biochemistry of drug resistance in infectious disease

Nonscientific interests: Photography, community work and spending time with my wife and daughter

I am a native of southwest Scotland and obtained my bachelor of science with honors (Class I) and Ph.D. from the University of Glasgow, United Kingdom. I first became interested in structural biology when I joined the group of professor David Barford at the Institute of Cancer Research in London, working on the structure of various human protein phosphatases. On completion of that post-doc, I took a position in the invasion and metastasis group run by professor Bradford Ozanne at the Beatson Institute for Cancer Research in Glasgow. This gave me the opportunity to use structural biology to complement an established and productive cell biology program that identifies and characterizes proteins promoting cancer cell invasion. In this study, we investigate the structural basis for the interaction between Lasp-1 and the Kelch domain of Krp1. This interaction is critical for actin rearrangment and the elongation of pseudopodia in our model of cell invasion. In addition to establishing the structural basis for this interaction, the crystal structure of the Krp1 Kelch domain proved very interesting, challenging the current definition of both the Kelch repeat and domain and demonstrating that this novel β-propeller incorporates a blade derived from non-Kelch sequence to provide the binding site for Lasp-1.

Read Gray's article on page 30498.