Contact Information:

(812) 855-4843
oakley@indiana.edu
Simon 320C

Martha Oakley received a B.A. at Carleton College University in 1986 and a B.A. at Oxford University in 1988. She was awarded her Ph.D. at California Institute of Technology in 1994.

Professor Oakley's lab is interested in two major areas, both involving specific recognition by proteins of biologically relevant ligands.

Research

My lab is interested in two major areas, both involving specific recognition by proteins of biologically relevant ligands. We take a multidisciplinary approach, combining techniques from biochemistry, molecular and cell biology, and organic chemistry to address these issues.

Coiled-coil proteins. The coiled coil is the most common protein-protein interaction motif in nature, occurring in a wide variety of proteins of medicinal and biological interest. Coiled coils consist of two or more a-helices, supercoiled around one another, that associate in a parallel or an antiparallel orientation. Recent structural studies have highlighted the importance of both parallel and antiparallel coiled coils in biology. Due to the prevalence of coiled-coil domains and to the recent explosion in genome sequence information, the ability to predict coiled-coil function from sequence data would be extremely valuable. Because the orientation within coiled coil affects strand pairing specificity, an understanding of the interactions that affect helix orientation is necessary to accurately predict interaction partners. We are using both protein design and random selection methods to address this issue, and we are applying the knowledge and techniques we have developed to the study of biologically important proteins containing antiparallel coiled coils.

Phosphatidylinositides. Phosphatidylinositides, such as PIP2 and PIP3, are key regulators for cytoskeletal dynamics, responses to hormones and growth factors, endocytosis, and apoptosis. These lipids bind specifically to target proteins and modulate their functions through largely unknown mechanisms. We are investigating the origins of specificity in the complexes between cytoskeletal regulatory proteins and PIP2 lipid assemblies, using polymeric PIP2 analogues. We are also using these analogues to investigate the mechanism by which PIP2 modulates the function of cytoskeletal proteins and of proteins involved in clathrin-mediated endocytosis. Finally, we are developing specific inhibitors for PIP2- or PIP3-modulated proteins for use as pharmaceutical agents or tools for in vivo research.

Publications

"The design of antiparallel coiled coils," with J. J. Hollenbeck. Curr. Opin. Struct. Biol., 11, 450 (2001).

"A GCN4 variant with a C-terminal basic region binds to DNA with wild-type affinity," with J. J. Hollenbeck, D. G. Gurnon, G. C. Fazio, and J. J. Carlson. Biochemistry, 40, 13833 (2001).

"Evaluation of the energetic contribution of interhelical coulombic interactions for coiled coil helix orientation specificity," with D. L. McClain and J. P. Binfet. J. Mol. Biol., 313, 371 (2001).

"Design and characterization of a heterodimeric coiled coil that forms exclusively with an antiparallel relative helix orientation," with D. L. McClain and H. L. Woods. J. Am. Chem. Soc., 123, 3151 (2001).

"GCN4 binds with high affinity to DNA sequences containing a single consensus half-site," with J. J. Hollenbeck. Biochemistry, 39, 6380 (2000).

"A buried polar interaction can direct the relative orientation of helices in a coiled coil," with P. S. Kim. Biochemistry, 37, 12603 (1998).

"Protein dissection of the antiparallel coiled coil from Escherichia coli seryl tRNA synthetase," with P. S. Kim. Biochemistry, 36, 2544 (1997).

"Structural motif of the GCN4 DNA binding domain characterized by affinity cleaving," with P. B. Dervan. Science, 248, 847 (1990).

"Synthesis of a hybrid protein containing the iron-binding ligand of bleomycin and the DNA-binding domain of Hin," with K. D. Turnbull and P. B. Dervan. Bioconjugate Chem., 5, 242, (1994).

"Only one of the two DNA-bound orientations of AP-1 found in solution cooperates with NFATp," with L. Chen, et al. Current Biol., 5, 882 (1995).

Awards

• Helen Hay Whitney Postdoctoral Fellow, Whitehead Institute for Biomedical Research, 1993-96
• National Science Foundation Faculty Early Career Development (CAREER) Award, 1997-2002
• Indiana University Teaching Excellence Recognition Award, 1999 and 2000.

Highlights