scholarly journals Interactions between nascent proteins and the ribosome surface inhibit co-translational folding

2021 ◽  
Author(s):  
Anaïs M. E. Cassaignau ◽  
Tomasz Włodarski ◽  
Sammy H. S. Chan ◽  
Lauren F. Woodburn ◽  
Ivana V. Bukvin ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Protein Engineering ◽  
Quantitative Agreement ◽  
Terminal Segment ◽  
Dynamic Mechanism ◽  
Native State ◽  
Folding Process

AbstractMost proteins begin to fold during biosynthesis on the ribosome. It has been suggested that interactions between the emerging polypeptide and the ribosome surface might allow the ribosome itself to modulate co-translational folding. Here we combine protein engineering and NMR spectroscopy to characterize a series of interactions between the ribosome surface and unfolded nascent chains of the immunoglobulin-like FLN5 filamin domain. The strongest interactions are found for a C-terminal segment that is essential for folding, and we demonstrate quantitative agreement between the strength of this interaction and the energetics of the co-translational folding process itself. Mutations in this region that reduce the extent of binding result in a shift in the co-translational folding equilibrium towards the native state. Our results therefore demonstrate that a competition between folding and binding provides a simple, dynamic mechanism for the modulation of co-translational folding by the ribosome.

KINETIC ANALYSIS OF PROTEIN FOLDING LATTICE MODELS

2004 ◽  
Vol 18 (04) ◽  
pp. 163-172 ◽  
Author(s):  
HU CHEN ◽  
XIN ZHOU ◽  
CHIH YOUNG LIAW ◽  
CHAN GHEE KOH
Keyword(s):  
Kinetic Model ◽  
Molten Globule ◽  
Lattice Models ◽  
Random Coil ◽  
Square Lattice ◽  
Energy Landscapes ◽  
Native State ◽  
Folding Process ◽  
Hp Model ◽  
Go Model

Based on two-dimensional square lattice models of proteins, the relation between folding time and temperature is studied by Monte Carlo simulation. The results can be represented by a kinetic model with three states — random coil, molten globule, and native state. The folding process is composed of nonspecific collapse and final searching for the native state. At high temperature, it is easy to escape from local traps in the folding process. With decreasing temperature, because of the trapping in local traps, the final searching speed decreases. Then the folding shows chevron rollover. Through the analysis of the fitted parameters of the kinetic model, it is found that the main difference between the energy landscapes of the HP model and the Go model is that the number of local minima of the Go model is less than that of the HP model.

Kinetic Stabilization of the Native State by Protein Engineering: Implications for Inhibition of Transthyretin Amyloidogenesis

2005 ◽  
Vol 347 (4) ◽  
pp. 841-854 ◽  
Author(s):  
Ted R. Foss ◽  
Matthew S. Kelker ◽  
R. Luke Wiseman ◽  
Ian A. Wilson ◽  
Jeffery W. Kelly
Keyword(s):  
Protein Engineering ◽  
Native State

scholarly journals Dramatic shape changes occur as Cytochrome c folds

2020 ◽  
Author(s):  
Serdal Kirmizialtin ◽  
Felicia Pitici ◽  
Alfredo E Cardenas ◽  
Ron Elber ◽  
D. Thirumalai
Keyword(s):  
Cytochrome C ◽  
Experimental Studies ◽  
Quantitative Agreement ◽  
Time Dependent ◽  
Native State ◽  
Time Resolved ◽  
Hydrophobic Collapse ◽  
Folding Mechanism ◽  
Cyt C ◽  
Shape Changes

AbstractExtensive experimental studies on the folding of Cytochrome c (Cyt c) make this small protein an ideal target for atomic detailed simulations for the purposes of quantitatively characterizing the structural transitions and the associated time scales for folding to the native state from an ensemble of unfolded states. We use previously generated atomically detailed folding trajectories by the Stochastic Difference Equation in Length (SDEL) to calculate the time-dependent changes in the Small Angle X-ray scattering (SAXS) profiles. Excellent agreement is obtained between experiments and simulations for the time dependent SAXS spectra, allowing us to identify the structures of the folding intermediates, which shows that Cyt c reaches the native state by a sequential folding mechanism. Using the ensembles of structures along the folding pathways we show that compaction and the sphericity of Cyt c change dramatically from the prolate ellipsoid shape in the unfolded state to the spherical native state. Our data, which provides unprecedented quantitative agreement with all aspects of time-resolved SAXS experiments, shows that hydrophobic collapse and amide group protection coincide on the 100 microseconds time scale, which is in accord with ultrafast Hydrogen/Deuterium exchange studies. Based on these results we propose that compaction of polypeptide chains, accompanied by dramatic shape changes, is a universal characteristic of globular proteins, regardless of the underlying folding mechanism.

scholarly journals Structure-Functional Insight into Transmembrane Helix Dimerization by Protein Engineering, Molecular Modeling and Heteronuclear NMR Spectroscopy

2012 ◽  
Vol 102 (3) ◽  
pp. 470a ◽  
Author(s):  
Eduard Bocharov ◽  
Pavel Volynsky ◽  
Konstantin Mineev ◽  
Dmitry Lesovoy ◽  
Kirill Nadezhdin ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Nmr Spectroscopy ◽  
Protein Engineering ◽  
Heteronuclear Nmr ◽  
Transmembrane Helix ◽  
Heteronuclear Nmr Spectroscopy ◽  
Insight Into

Pathway and stability of protein folding

1991 ◽  
Vol 332 (1263) ◽  
pp. 171-176 ◽  
Keyword(s):  
Protein Folding ◽  
Protein Engineering ◽  
Hydrogen Exchange ◽  
Hydrophobic Core ◽  
Wild Type ◽  
Kinetic Measurements ◽  
Mutant Proteins ◽  
Folding Process ◽  
Β Sheet

We describe an experimental approach to the problem of protein folding and stability which measures interaction energies and maps structures of intermediates and transition states during the folding pathway. The strategy is based on two steps. First, protein engineering is used to remove interactions that stabilize defined positions in barnase, the RNAse from Bacillus amyloliquefaciens . The consequent changes in stability are measured from the changes in free energy of unfolding of the protien. Second, each mutation is used as a probe of the structure around the wild-type side chain during the folding process. Kinetic measurements are made on the folding and unfolding of wild-type and mutant proteins. The kinetic and thermodynamic data are combined and analysed to show the role of individual side chains in the stabilization of the folded, transition and intermediate states of the protein. The protein engineering experiments are corroborated by nuclear magnetic resonance studies of hydrogen exchange during the folding process. Folding is a multiphasic process in which α-helices and β-sheet are formed relatively early. Formation of the hydrophobic core by docking helix and sheet is (partly) rate determining. The final steps involve the forming of loops and the capping of the N-termini of helices.

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