A dynamic model of long-range conformational adaptations triggered by nucleotide binding in GroEL-GroES

Proteins
Lars SkjaervenAurora Martinez

Abstract

The molecular chaperone, GroEL, essential for correct protein folding in E. coli, is composed of 14 identical subunits organized in two interacting rings, each providing a folding chamber for non-native substrate proteins. The oligomeric assembly shows positive cooperativity within each ring and negative cooperativity between the rings. Although it is well known that ATP and long-range allosteric interactions drive the functional cycle of GroEL, an atomic resolution view of how ligand binding modulates conformational adaptations over long distances remains a major challenge. Moreover, little is known on the relation between equilibrium dynamics at physiological temperatures and the allosteric transitions in GroEL. Here we present multiple all-atom molecular dynamics simulations of the GroEL-GroES assemblies at different stages of the functional cycle. Combined with an extensive analysis of the complete set of experimentally available structures, principal component analysis and conformer plots, we provide an explicit evaluation of the accessible conformational space of unliganded GroEL. Our results suggest the presence of pre-existing conformers at the equatorial domain level, and a shift of the conformational ensemble upon ATP...Continue Reading

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Citations

Jul 5, 2015·FEBS Letters·Lars SkjærvenJosé María Valpuesta
Oct 17, 2017·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Jayvee R AbellaLydia E Kavraki
Oct 1, 2014·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Robert J TomanekCecilia W Lo
Oct 3, 2018·The Journal of Physical Chemistry. B·Stefano Piana, David E Shaw

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