multi-scale simulations provide supporting evidence for the hypothesis of intramolecular protein translocation in groelgroes complexes多尺度模拟提供支持假说的证据在groelgroes复合物分子内蛋白质易位.pdfVIP

Multi-Scale Simulations Provide Supporting Evidence for the Hypothesis of Intramolecular Protein Translocation in GroEL/GroES Complexes 1 1 2 1,3 Ivan Coluzza *, Alfonso De Simone , Franca Fraternali , Daan Frenkel 1 Department of Chemistry, University of Cambridge, Cambridge, United Kingdom, 2 Randall Division of Cell and Molecular Biophysics, King’s College London, London, United Kingdom, 3 FOM Institute AMOLF, Amsterdam, The Netherlands Abstract The biological function of chaperone complexes is to assist the folding of non-native proteins. The widely studied GroEL chaperonin is a double-barreled complex that can trap non-native proteins in one of its two barrels. The ATP-driven binding of a GroES cap then results in a major structural change of the chamber where the substrate is trapped and initiates a refolding attempt. The two barrels operate anti-synchronously. The central region between the two barrels contains a high concentration of disordered protein chains, the role of which was thus far unclear. In this work we report a combination of atomistic and coarse-grained simulations that probe the structure and dynamics of the equatorial region of the GroEL/GroES chaperonin complex. Surprisingly, our simulations show that the equatorial region provides a translocation channel that will block the passage of folded proteins but allows the passage of secondary units with the diameter of an alpha-helix. We compute the free-energy barrier that has to be overcome during translocation and find that it can easily be crossed under the influence of thermal fluctuations. Hence, strongly non-native proteins can be squeezed like toothpaste from one barrel to the next where they will refold. Proteins that are a