Helix-Coil Transition at a Glycine following a Nascent α-Helix: A Synergetic Guidance Mechanism for Helix Growth

Pal, S and Banerjee, S and Prabhakaran, EN (2020) Helix-Coil Transition at a Glycine following a Nascent α-Helix: A Synergetic Guidance Mechanism for Helix Growth. In: Journal of Physical Chemistry A, 124 (37). pp. 7478-7490.

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Abstract

A detailed understanding of forces guiding the rapid folding of a polypeptide from an apparently random coil state to an ordered α-helical structure following the rate-limiting preorganization of the initial three residue backbones into helical conformation is imperative to comprehending and regulating protein folding and for the rational design of biological mimetics. However, several details of this process are still unknown. First, although the helix-coil transition was proposed to originate at the residue level (J. Chem. Phys. 1959, 31, 526-535; J. Chem. Phys. 1961, 34, 1963-1974), all helix-folding studies have only established it between time-averaged bulk states of a long-lived helix and several transiently populated random coils, along the whole helix model sequence. Second, the predominant thermodynamic forces driving either this two-state transition or the faster helix growth following helix nucleation are still unclear. Third, the conformational space of the random coil state is not well-defined unlike its corresponding α-helix. Here we investigate the restrictions placed on the conformational space of a Gly residue backbone, as a result of it immediately succeeding a nascent α-helical turn. Analyses of the temperature-dependent 1D-, 2D-NMR, FT-IR, and CD spectra and GROMACS MD simulation trajectory of a Gly residue backbone following a model α-helical turn, which is artificially rigidified by a covalent hydrogen bond surrogate, reveal that: (i) the α-helical turn guides the � torsion of the Gly exclusively into either a predominantly populated entropically favored α-helical (α-�) state or a scarcely populated random coil (RC-�) state; (ii) the α-� state of Gly in turn favors the stability of the preceding α-helical turn, while the RC-� state disrupts it, revealing an entropy-driven synergetic guidance for helix growth in the residue following helix nucleation. The applicability of a current synergetic guidance mechanism to explain rapid helix growth in folded and unfolded states of proteins and helical peptides is discussed. © Copyright © 2020 American Chemical Society.

Item Type:	Journal Article
Publication:	Journal of Physical Chemistry A
Publisher:	American Chemical Society
Additional Information:	Copyright to this article belongs to American Chemical Society
Keywords:	Amino acids; Crystallization; Hydrogen bonds; Nuclear magnetic resonance spectroscopy; Nucleation, Conformational space; Helical conformation; Helical structures; Helix-coil transitions; Random coil state; Temperature dependent; Thermodynamic forces; Two-state transitions, Proteins
Department/Centre:	Division of Chemical Sciences > Organic Chemistry
Date Deposited:	06 Jan 2021 06:03
Last Modified:	06 Jan 2021 06:03
URI:	http://eprints.iisc.ac.in/id/eprint/66795

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