Exploration of partially unfolded states of human α-lactalbumin by molecular dynamics simulation11Edited by B. Honig

2001 ◽  
Vol 306 (2) ◽  
pp. 329-347 ◽  
Author(s):  
Emanuele Paci ◽  
Lorna J. Smith ◽  
Christopher M. Dobson ◽  
Martin Karplus
Keyword(s):  
Molecular Dynamics ◽  
Partially Unfolded ◽  
Partially Unfolded States

Replica Exchange Molecular Dynamics Simulations Reveal Self-association Sites in M- Crystallin Caused by Mutations Provide Insights of Cataract

2021 ◽  
Author(s):  
Sunita Patel ◽  
Ramakrishna V. Hosur
Keyword(s):  
Molecular Dynamics ◽  
Protein Solubility ◽  
Replica Exchange ◽  
Eye Lens ◽  
Hydrophobic Core ◽  
Lens Crystallins ◽  
Replica Exchange Molecular Dynamics ◽  
Partially Unfolded ◽  
Dynamics Simulations ◽  
Partially Unfolded States

Abstract Crystallins are ubiquitous, however, prevalence is seen in eye lens. Eye lens crystallins are long-lived and structural intactness is required for maintaining lens transparency and protein solubility. Mutations in crystallin often lead to cataract. In this study, we performed mutations at specific sites of M-crystallin, a close homologue of eye lens crystallin and studied by employing replica exchange molecular dynamics with generalized Born solvation model. Mutations were made on the Ca2+ binding residues (K34D and S77D) and in the hydrophobic core (W45R) which is known to cause congenital cataract in homologous γD-crystallin. The chosen mutations caused large motion of the N-terminal Greek key, concomitantly break the interlocking Greek keys interactions and perturbed the compact core resulting in several folded and partially unfolded states. Partially unfolded states expose large hydrophobic patches that can act as precursors for self-aggregation. Accumulation of such aggregates is the potential cause of cataract in homologous crystallins.

scholarly journals Replica exchange molecular dynamics simulations reveal self-association sites in M-crystallin caused by mutations provide insights of cataract

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sunita Patel ◽  
Ramakrishna V. Hosur
Keyword(s):  
Molecular Dynamics ◽  
Dynamics Simulation ◽  
Replica Exchange ◽  
Eye Lens ◽  
Hydrophobic Core ◽  
Lens Crystallins ◽  
Replica Exchange Molecular Dynamics ◽  
Solvent Model ◽  
Partially Unfolded ◽  
Partially Unfolded States

AbstractCrystallins are ubiquitous, however, prevalence is seen in eye lens. Eye lens crystallins are long-lived and structural intactness is required for maintaining lens transparency and protein solubility. Mutations in crystallins often lead to cataract. In this study, we performed mutations at specific sites of M-crystallin, a close homologue of eye lens crystallin and studied by using replica exchange molecular dynamics simulation with generalized Born implicit solvent model. Mutations were made on the Ca2+ binding residues (K34D and S77D) and in the hydrophobic core (W45R) which is known to cause congenital cataract in homologous γD-crystallin. The chosen mutations caused large motion of the N-terminal Greek key, concomitantly broke the interlocking Greek keys interactions and perturbed the compact core resulting in several folded and partially unfolded states. Partially unfolded states exposed large hydrophobic patches that could act as precursors for self-aggregation. Accumulation of such aggregates is the potential cause of cataract in homologous eye lens crystallins.

scholarly journals Mechanism of the small ATP-independent chaperone Spy is substrate specific

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rishav Mitra ◽  
Varun V. Gadkari ◽  
Ben A. Meinen ◽  
Carlo P. M. van Mierlo ◽  
Brandon T. Ruotolo ◽  
...  
Keyword(s):  
Relative Affinity ◽  
Complex Protein ◽  
Partially Unfolded ◽  
Substrate Proteins ◽  
Partially Unfolded States

AbstractATP-independent chaperones are usually considered to be holdases that rapidly bind to non-native states of substrate proteins and prevent their aggregation. These chaperones are thought to release their substrate proteins prior to their folding. Spy is an ATP-independent chaperone that acts as an aggregation inhibiting holdase but does so by allowing its substrate proteins to fold while they remain continuously chaperone bound, thus acting as a foldase as well. The attributes that allow such dual chaperoning behavior are unclear. Here, we used the topologically complex protein apoflavodoxin to show that the outcome of Spy’s action is substrate specific and depends on its relative affinity for different folding states. Tighter binding of Spy to partially unfolded states of apoflavodoxin limits the possibility of folding while bound, converting Spy to a holdase chaperone. Our results highlight the central role of the substrate in determining the mechanism of chaperone action.

Detecting and exploring partially unfolded states of proteins using a sensor with chaperone bound to its surface

2008 ◽  
Vol 24 (4) ◽  
pp. 963-969 ◽  
Author(s):  
Doaa F. George ◽  
Marcela M.M. Bilek ◽  
David R. McKenzie
Keyword(s):  
Partially Unfolded ◽  
Partially Unfolded States

MINOES: A new approach to select a representative ensemble of structures in NMR studies of (partially) unfolded states. Application to Δ25-PYP

2009 ◽  
Vol 74 (4) ◽  
pp. 895-904 ◽  
Author(s):  
Mickaël Krzeminski ◽  
Gloria Fuentes ◽  
Rolf Boelens ◽  
Alexandre M.J.J. Bonvin
Keyword(s):  
Nmr Studies ◽  
New Approach ◽  
Partially Unfolded ◽  
Partially Unfolded States

Partially Unfolded States of β2-Microglobulin and Amyloid Formation in Vitro†

Biochemistry ◽  
2000 ◽  
Vol 39 (30) ◽  
pp. 8735-8746 ◽  
Author(s):  
Victoria J. McParland ◽  
Neil M. Kad ◽  
Arnout P. Kalverda ◽  
Anthony Brown ◽  
Patricia Kirwin-Jones ◽  
...  
Keyword(s):  
Amyloid Formation ◽  
Β2 Microglobulin ◽  
Partially Unfolded ◽  
Partially Unfolded States

Describing Partially Unfolded States of Proteins from Sparse NMR Ddata

2005 ◽  
Vol 33 (3) ◽  
pp. 175-186 ◽  
Author(s):  
Gloria Fuentes ◽  
Aart J. Nederveen ◽  
Robert Kaptein ◽  
Rolf Boelens ◽  
Alexandre M. J. J. Bonvin
Keyword(s):  
Partially Unfolded ◽  
Partially Unfolded States
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