The Experts below are selected from a list of 141426 Experts worldwide ranked by ideXlab platform

Toshio Ando - One of the best experts on this subject based on the ideXlab platform.

Daisuke Noshiro - One of the best experts on this subject based on the ideXlab platform.

Manajit Hayerhartl - One of the best experts on this subject based on the ideXlab platform.

  • groel ring separation and exchange in the chaperonin reaction
    Cell, 2018
    Co-Authors: Astrid Bracher, Goran Milicic, Ulrich F Hartl, Amit Singh, Manajit Hayerhartl
    Abstract:

    Summary The bacterial chaperonin GroEL and its cofactor, GroES, form a nano-cage for a single molecule of substrate protein (SP) to fold in isolation. GroEL and GroES undergo an ATP-regulated Interaction Cycle to close and open the folding cage. GroEL consists of two heptameric rings stacked back to back. Here, we show that GroEL undergoes transient ring separation, resulting in ring exchange between complexes. Ring separation occurs upon ATP-binding to the trans ring of the asymmetric GroEL:7ADP:GroES complex in the presence or absence of SP and is a consequence of inter-ring negative allostery. We find that a GroEL mutant unable to perform ring separation is folding active but populates symmetric GroEL:GroES 2 complexes, where both GroEL rings function simultaneously rather than sequentially. As a consequence, SP binding and release from the folding chamber is inefficient, and E. coli growth is impaired. We suggest that transient ring separation is an integral part of the chaperonin mechanism.

  • chaperonin assisted protein folding relative population of asymmetric and symmetric groel groes complexes
    Journal of Molecular Biology, 2015
    Co-Authors: Shubhasis Haldar, Amit J Gupta, Goran Milicic, Ulrich F Hartl, Manajit Hayerhartl
    Abstract:

    Abstract The chaperonin GroEL, a cylindrical complex consisting of two stacked heptameric rings, and its lid-like cofactor GroES form a nano-cage in which a single polypeptide chain is transiently enclosed and allowed to fold unimpaired by aggregation. GroEL and GroES undergo an ATP-regulated Interaction Cycle that serves to close and open the folding cage. Recent reports suggest that the presence of non-native substrate protein alters the GroEL/ES reaction by shifting it from asymmetric to symmetric complexes. In the asymmetric reaction mode, only one ring of GroEL is GroES bound and the two rings function sequentially, coupled by negative allostery. In the symmetric mode, both GroEL rings are GroES bound and are folding active simultaneously. Here, we find that the results of assays based on fluorescence resonance energy transfer recently used to quantify symmetric complexes depend strongly on the fluorophore pair used. We therefore developed a novel assay based on fluorescence cross-correlation spectroscopy to accurately measure GroEL:GroES stoichiometry. This assay avoids fluorophore labeling of GroEL and the use of GroEL cysteine mutants. Our results show that symmetric GroEL:GroES 2 complexes are substantially populated only in the presence of non-foldable model proteins, such as α-lactalbumin and α-casein, which “over-stimulate” the GroEL ATPase and uncouple the negative GroEL inter-ring allostery. In contrast, asymmetric complexes are dominant both in the absence of substrate and in the presence of foldable substrate proteins. Moreover, uncoupling of the GroEL rings and formation of symmetric GroEL:GroES 2 complexes is suppressed at physiological ATP:ADP concentration. We conclude that the asymmetric GroEL:GroES complex represents the main folding active form of the chaperonin.

Kevin Kjoller - One of the best experts on this subject based on the ideXlab platform.

  • direct measurement of tapping force with a cantilever deflection force sensor
    Ultramicroscopy, 2004
    Co-Authors: Chanmin Su, Lin Huang, Kevin Kjoller
    Abstract:

    Abstract An experimental set up dedicated to the measurement of atomic force microscope tapping force was developed. In the set-up, a standard TappingMode™ probe cantilever was used to tap another cantilever equipped with its own low noise and high sensitivity deflection detection system for force measurement. The amplitude and phase change of the tapping lever as well as the deflection of the sensing lever were simultaneously recorded as a function of tip/surface separation. Since the deflection of the sensing cantilever reflects the average force over one Interaction Cycle, we measured the total average force quantitatively after calibrating the spring constant and deflection sensitivity of the sensing lever. Considerable effort was made to achieve the same force curve in the tapping force measurement as occur during imaging of conventional samples such that the detected tapping force reflects the same Interaction of the imaging process.

Ulrich F Hartl - One of the best experts on this subject based on the ideXlab platform.

  • groel ring separation and exchange in the chaperonin reaction
    Cell, 2018
    Co-Authors: Astrid Bracher, Goran Milicic, Ulrich F Hartl, Amit Singh, Manajit Hayerhartl
    Abstract:

    Summary The bacterial chaperonin GroEL and its cofactor, GroES, form a nano-cage for a single molecule of substrate protein (SP) to fold in isolation. GroEL and GroES undergo an ATP-regulated Interaction Cycle to close and open the folding cage. GroEL consists of two heptameric rings stacked back to back. Here, we show that GroEL undergoes transient ring separation, resulting in ring exchange between complexes. Ring separation occurs upon ATP-binding to the trans ring of the asymmetric GroEL:7ADP:GroES complex in the presence or absence of SP and is a consequence of inter-ring negative allostery. We find that a GroEL mutant unable to perform ring separation is folding active but populates symmetric GroEL:GroES 2 complexes, where both GroEL rings function simultaneously rather than sequentially. As a consequence, SP binding and release from the folding chamber is inefficient, and E. coli growth is impaired. We suggest that transient ring separation is an integral part of the chaperonin mechanism.

  • chaperonin assisted protein folding relative population of asymmetric and symmetric groel groes complexes
    Journal of Molecular Biology, 2015
    Co-Authors: Shubhasis Haldar, Amit J Gupta, Goran Milicic, Ulrich F Hartl, Manajit Hayerhartl
    Abstract:

    Abstract The chaperonin GroEL, a cylindrical complex consisting of two stacked heptameric rings, and its lid-like cofactor GroES form a nano-cage in which a single polypeptide chain is transiently enclosed and allowed to fold unimpaired by aggregation. GroEL and GroES undergo an ATP-regulated Interaction Cycle that serves to close and open the folding cage. Recent reports suggest that the presence of non-native substrate protein alters the GroEL/ES reaction by shifting it from asymmetric to symmetric complexes. In the asymmetric reaction mode, only one ring of GroEL is GroES bound and the two rings function sequentially, coupled by negative allostery. In the symmetric mode, both GroEL rings are GroES bound and are folding active simultaneously. Here, we find that the results of assays based on fluorescence resonance energy transfer recently used to quantify symmetric complexes depend strongly on the fluorophore pair used. We therefore developed a novel assay based on fluorescence cross-correlation spectroscopy to accurately measure GroEL:GroES stoichiometry. This assay avoids fluorophore labeling of GroEL and the use of GroEL cysteine mutants. Our results show that symmetric GroEL:GroES 2 complexes are substantially populated only in the presence of non-foldable model proteins, such as α-lactalbumin and α-casein, which “over-stimulate” the GroEL ATPase and uncouple the negative GroEL inter-ring allostery. In contrast, asymmetric complexes are dominant both in the absence of substrate and in the presence of foldable substrate proteins. Moreover, uncoupling of the GroEL rings and formation of symmetric GroEL:GroES 2 complexes is suppressed at physiological ATP:ADP concentration. We conclude that the asymmetric GroEL:GroES complex represents the main folding active form of the chaperonin.