Evolutionary conservation of amino acids contributing to the protein folding transition state

Chong, Song; Ham, Sihyun

doi:10.1002/jcc.27060

Cited by 2 publications

(2 citation statements)

References 49 publications

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“…Interestingly, the I37 residue, which is involved in 2 of the 3 "first-entangling" contacts without being part of the ice-binding surface, is found to be conserved as well [77]. However, a more careful analysis should gauge the contribution to residue conservation from overall stability, since there is currently no evidence of residue conservation due to kinetic reasons for small non-entangled fast folding proteins [82].…”

Section: Discussionmentioning

confidence: 99%

Folding kinetics of an entangled protein

Salicari,

Baiesi,

Orlandini

et al. 2023

PLoS Comput Biol

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The possibility of the protein backbone adopting lasso-like entangled motifs has attracted increasing attention. After discovering the surprising abundance of natively entangled protein domain structures, it was shown that misfolded entangled subpopulations might become thermosensitive or escape the homeostasis network just after translation. To investigate the role of entanglement in shaping folding kinetics, we introduce a novel indicator and analyze simulations of a coarse-grained, structure-based model for two small single-domain proteins. The model recapitulates the well-known two-state folding mechanism of a non-entangled SH3 domain. However, despite its small size, a natively entangled antifreeze RD1 protein displays a rich refolding behavior, populating two distinct kinetic intermediates: a short-lived, entangled, near-unfolded state and a longer-lived, non-entangled, near-native state. The former directs refolding along a fast pathway, whereas the latter is a kinetic trap, consistently with known experimental evidence of two different characteristic times. Upon trapping, the natively entangled loop folds without being threaded by the N-terminal residues. After trapping, the native entangled structure emerges by either backtracking to the unfolded state or threading through the already formed but not yet entangled loop. Along the fast pathway, trapping does not occur because the native contacts at the closure of the lasso-like loop fold after those involved in the N-terminal thread, confirming previous predictions. Despite this, entanglement may appear already in unfolded configurations. Remarkably, a longer-lived, near-native intermediate, with non-native entanglement properties, recalls what was observed in cotranslational folding.

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Section: Discussionmentioning

confidence: 99%

Folding kinetics of an entangled protein

Salicari,

Baiesi,

Orlandini

et al. 2023

PLoS Comput Biol

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“…The recent advances in molecular dynamics (MD) simulation techniques are remarkable [37,38], and relatively large proteins have become targets of MD simulations. However, a target of an MD simulation tends to be limited to a relatively small protein for analyses of the folding of proteins [39][40][41]. Concerning globin proteins, the applications of MD techniques are limited to the dynamics of native structures [42,43].…”

Section: Computational Analyses On Globin Proteinsmentioning

confidence: 99%

Non-Native Structures of Apomyoglobin and Apoleghemoglobin in Folding Intermediates Related to the Protein Misfolding

Nishimura

Kikuchi

2023

Molecules

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Protein folding is essential for a polypeptide chain to acquire its proper structure and function. Globins are a superfamily of ubiquitous heme-binding α-helical proteins whose function is principally to regulate oxygen homoeostasis. In this review, we explore the hierarchical helical formation in the globin proteins apomyoglobin and leghemoglobin, and we discuss the existence of non-native and misfolded structures occurring during the course of folding to its native state. This review summarizes the research aimed at characterizing and comparing the equilibrium and kinetic intermediates, as well as delineating the complete folding pathway at a molecular level, in order to answer the following questions: “What is the mechanism of misfolding via a folding intermediate? Does the non-native structure stabilize the contemporary intermediate structure? Does the non-native structure induce slower folding?” The role of the non-native structures in the folding intermediate related to misfolding is also discussed.

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Evolutionary conservation of amino acids contributing to the protein folding transition state

Cited by 2 publications

References 49 publications

Folding kinetics of an entangled protein

Folding kinetics of an entangled protein

Non-Native Structures of Apomyoglobin and Apoleghemoglobin in Folding Intermediates Related to the Protein Misfolding

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