PS Seminar Series: Optimizing protein folding with a parallel processing, iterative annealing machine


Abstract - The GroE chaperonins assist substrate protein (SP) folding by cycling through several conformational states, driven ultimately by the hydrolysis of ATP. With each cycle the SP is, in turn, captured, unfolded, briefly encapsulated (t1/2 ~1 s), and released by the chaperonin complex. Only a small fraction (~1%) of the transiently encapsulated SP is released in the native state with each cycle. In the absence of SP the two rings of GroEL are alternately functional, the asymmetric GroEL2:GroES1 is the predominant species and the release of the product ADP is rate-determining. But in the presence of SP a dramatic change in the kinetic mechanism occurs. SP catalyzes the release of the product ADP, the hydrolysis of ATP becomes the rate-determining step and the symmetric GroEL2:GroES2 is the predominant species. The residence half-time of the SP and GroES on a GroEL ring is reduced to ~1 s. Both rings of GroEL function simultaneously and multiple iterations are required to completely fold the SP. The chaperonins are thus parallel-processing, iterative annealing machines. The operation of the symmetric chaperonin cycle involves the breakage of symmetry, the stochastic hydrolysis of ATP in both GroEL rings that leads to the dissociation of one or other GroES and the encapsulated SP; the generation of asymmetry from symmetry.


1998- present: Distinguished University Professor, Department of Chemistry & Biochenistry, Institute of Physical Science and Technology, University of Maryland;

1978-97 Principal Investigator, later Research Leader, then DuPont Fellow, Central Research and Development Department, DuPont Co,Delaware;

1977-78: Scientist, Institut für Biochemie der GSF, Munich;

1974-77: Research Fellow, Research School of Biological Science, Australian Nat. University,

1972-74: Post-doctoral Fellow, MaxPlanck Gesellschaft, Berlin;

1965-66: High School Teacher, Scotland

Date & time

1–2pm 22 November 2017


Robertson Lecture Theatre, Robertson Building (46), ANU


Prof George Lorimer (Distinguished University Professor), University of Maryland


 Gagan Bhardwaj
 02 6125 9395

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