Richard Anderson Lab

Research: Structure and Function of Signaling Molecules

Figure 1

Structure of the PIPIIB enzyme. Top, ribbon structure of PIPIIB looking up from the membrane. Middle, a space filling model of the PIPIIB docked on a membrane. A model showing the oreintaton of Mg-ATP and the substrate PI5P.

My group and I have had long term interest in the structure and function of signaling molecules. Although we do not solve 3-D structures of signaling molecules our selves, my group and I use structural data to define cellular functions and signaling mechanisms. As an example (see Figure) is the structure of the type II PI5P 4-kinase beta (PIPIIβ), we biochemically isolated and cloned this enzyme and worked with Jim Hurley at the NIH (now at Berkely) to solve the structure(Cell 94, 829-839). From this structure, we defined the mechanism for substrate usage and lipid messenger generation by making structure designed changes in the enzyme(Mol. Cell 5, 1–11). This structure function approach is a continuing emphasis in my laboratory, currently with many proteins and enzymes that we want to collaboratively define structures and use these structures to elucidate enzymatic and biological mechanims to address functional aspects. In each of the three current NIH funded projects we have a continuing structure/function emphasis.

 

The structures of Star-PAP, LAPTM4B, PIPKIg isoforms, and complexes between PIPKI isoforms and interacting effectors would be of great interest to us and with strong translational significance.