Mechanistic Basis of Oscillation in a Three-Protein Circadian Clock

1. UIC WISEST 2007-2008 VISITING SCHOLARS PROGRAM Mechanistic Basis of Oscillation in a Three-Protein Circadian Clock Biological Sciences Chemistry Earth & Environmental Sciences Physics Bioengineering Chemical Engineering Civil & Materials Engineering Computer Science Electrical & Computer Engineering Mechanical & Industrial Engineering Mathematics, Statistics & Computer Science Dr. Erin O’Shea Professor of Molecular & Cellular Biology, Chemistry, & Chemical Biology Harvard University Investigator, Howard Hughes Medical Institute Director, FAS Center for Systems Biology 1:00 PM, Tuesday, March 18, 2008, SES 230 ABSTRACT The simple circadian oscillator found in cyanobacteria can be reconstituted in vitro using three proteins-KaiA, KaiB and KaiC.  The total phosphorylation level of KaiC oscillates with a circadian period, but the mechanism underlying its sustained oscillation remains unclear.  Here we show that four forms of KaiC differing in their phosphorylation state appear in an ordered pattern arising from the intrinsic autokinase and autophosphatase rates of KaiC and their modulation by KaiA.  Kinetic and biochemical data indicate that one of these phosphoforms inhibits the activity of KaiA via interaction with KaiB, providing the crucial feedback that sustains oscillation. A mathematical model constrained by experimental data quantitatively reproduces the circadian period and the distinctive dynamics of the four phosphoforms. DETAILS Lecture March 18, 1:00 – 2:00 PM, SES 230 Presented by the Chemistry Department in partnership with the Women in Science & Engineering System Transformation (WISEST) Program. Sponsored by an NSF ADVANCE Institutional Transformation Award