2004 ASBMB Fellowship: Janet Deane

Janet Deane I commenced my Bachelor of Medical Science degree in 1997 at the University of Sydney, not certain whether I was more interested in a career in science or medicine. Throughout my undergraduate years I became increasingly interested in biochemistry. After completing my honours degree in Jacqui Matthews' lab I was convinced that a PhD in biochemistry was what I wanted to do. The research I have conducted in Jacqui's lab has consisted of looking at the interaction between two transcriptional regulators, LMO4 and ldb1. LMO4 is a member of a small family of nuclear transcriptional regulators and has recently been shown to be overexpressed in over 50% of primary breast cancers. LMO4 interacts specifically with several proteins, including ldb1, via its LIM domains. As it was not known how LIM domains interact with their partner proteins we wanted to determine the structure of a complex formed by LMO4 and ldb1. By creating fusion proteins containing the interacting domains of LMO4 and ldb1, I was able to successfully purify intramolecular complexes of these proteins. During my PhD I have used NMR spectroscopy to solve the structure of the N-terminal LIM domain of LMO4 bound to the LID domain of ldb1. The structure of this complex revealed details of the interaction that allowed the subsequent design of a larger complex that included both LIM domains of LMO4. This larger complex was successfully crystallised for X-ray diffraction experiments. Multiple anomalous dispersion (MAD) data to 1.3Ã… resolution was collected at the synchrotron in Stanford, USA. Using these data I was able to solve the X-ray structure of this LMO4:ldb1 complex. Analysis of these structures suggests a mechanism by which ldb1 can bind LMO4 specifically, and LIM domains from LMO and LIM homeodomain proteins in general. The ASBMB fellowship will allow me to travel to Lund University in Sweden to carry out other X-ray diffraction experiments at the synchrotron facilities at MAX-lab.

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This page last modified: October 10, 2008.