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Spontaneous conformational changes in the E. coli GroEL subunit from all-atom molecular dynamics simulations
Please use this identifier to cite or link to this item:
http://hdl.handle.net/1860/2577
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| Title: | Spontaneous conformational changes in the E. coli GroEL subunit from all-atom molecular dynamics simulations |
| Authors: | Sliozberg, Yelena R.
Abrams, Cameron F. |
| Issue Date: | Sep-2007 |
| Publisher: | Biophysical Society |
| Citation: | Biophysical Journal, 93(6): pp. 1906-1916. |
| Abstract: | The Escherichia coli chaperonin GroEL is a complex of identical subunit proteins (57 kDa each) arranged in a backto-
back stacking of two heptameric rings. Its hallmarks include nested positive intra-ring and negative inter-ring cooperativity in
adenosine trisphosphate (ATP) binding and the ability to mediate the folding of newly transcribed and/or denatured substrate
proteins. We performed unbiased molecular dynamics simulations of the GroEL subunit protein in explicit water both with and
without the nucleotide KMgATP to understand better the details of the structural transitions that enable these behaviors. Placing
KMgATP in the equatorial domain binding pocket of a t state subunit, which corresponds to a low ATP-affinity state, produced a
short-lived (6 ns) state that spontaneously transitioned to the high ATP-affinity r state. The important feature of this transition is a
large-scale rotation of the intermediate domain’s helix M to close the ATP binding pocket. Pivoting of helix M is accompanied by
counterclockwise rotation and slight deformation of the apical domain, important for lowering the affinity for substrate protein.
Aligning simulation conformations into model heptamer rings demonstrates that the t/r transition in one subunit is not sterically
hindered by t state neighbors, but requires breakage of Arg197-Glu386 intersubunit salt bridges, which are important for inter-ring
positive cooperativity. Lowest-frequency quasi-harmonic modes of vibration computed pre- and post-transition clearly show that
natural vibrations facilitate the transition. Finally, we propose a novel mechanism for inter-ring cooperativity in ATP binding inspired
by the observation of spontaneous insertion of the side chain of Ala480 into the empty nucleotide pocket. |
| URI: | http://dx.doi.org/10.1529/biophysj.107.108043
http://hdl.handle.net/1860/2577 |
| Appears in Collections: | Faculty Research and Publications (CBE)
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