β-sheets Mediate the Conformational Change and Allosteric Signal Transmission Between the AsLOV2 Termini

Overview

Journal J Comput Chem

Publisher Wiley

Specialties Biology
Chemistry

Date 2024 Mar 13

PMID 38476039

Authors

Sian Xiao

Mayar Tarek Ibrahim

Gennady M Verkhivker

Brian D Zoltowski

Peng Tao

Affiliations

Soon will be listed here.

Abstract

Avena sativa phototropin 1 light-oxygen-voltage 2 domain (AsLOV2) is a model protein of Per-Arnt-Sim (PAS) superfamily, characterized by conformational changes in response to external environmental stimuli. This conformational change begins with the unfolding of the N-terminal A'α helix in the dark state followed by the unfolding of the C-terminal Jα helix. The light state is characterized by the unfolded termini and the subsequent modifications in hydrogen bond patterns. In this photoreceptor, β-sheets are identified as crucial components for mediating allosteric signal transmission between the two termini. Through combined experimental and computational investigations, the Hβ and Iβ strands are recognized as the most critical and influential β-sheets in AsLOV2's allosteric mechanism. To elucidate the role of these β-sheets, we introduced 13 distinct mutations (F490L, N492A, L493A, F494L, H495L, L496F, Q497A, R500A, F509L, Q513A, L514A, D515V, and T517V) and conducted comprehensive molecular dynamics simulations. In-depth hydrogen bond analyses emphasized the role of two hydrogen bonds, Asn482-Leu453 and Gln479-Val520, in the observed distinct behaviors of L493A, L496F, Q497A, and D515V mutants. This illustrates the role of β-sheets in the transmission of the allosteric signal upon the photoactivation of the light state.

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