The Amino-Terminal Helix Modulates Light-Activated Conformational Changes in AsLOV2

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• 作者：Josiah P. Zayner¹ ; Chloe Antoniou¹ ; Tobin R. Sosnick¹ ; ² ; ^{trsosnic@uchicago.edu}
• 关键词：LOV ; light-oxygen-voltage ; PAS ; Per-Arnt-Sim ; FMN ; flavin mononucleotide ; FTIR ; Fourier transform infrared ; WT ; wild type ; CPMG ; Carr&ndash ; Purcell&ndash ; Meiboom&ndash ; Gill ; HSQC ; heteronuclear single quantum coherence ; biHis ; bihistidine ; MD ; molecular d
• 刊名：Journal of Molecular Biology
• 出版年：2012
• 期刊代码：102_00222836
• 类别：imm
• 出版时间：25 May, 2012
• 卷：419
• 期：1-2
• 页码：61-74
• 文件大小：1786 K

摘要

The mechanism of light-triggered conformational change and signaling in light-oxygen-voltage (LOV) domains remains elusive in spite of extensive investigation and their use in optogenetic studies. The LOV2 domain of Avena sativa phototropin 1 (AsLOV2), a member of the Per-Arnt-Sim (PAS) family, contains a flavin mononucleotide chromophore that forms a covalent bond with a cysteine upon illumination. This event leads to the release of the carboxy-terminal J伪 helix, the biological output signal. Using mutational analysis, circular dichroism, and NMR, we find that the largely ignored amino-terminal helix is a control element in AsLOV2's light-activated conformational change. We further identify a direct amino-to-carboxy-terminal 鈥渋nput-output鈥?signaling pathway. These findings provide a framework to rationalize the LOV domain architecture, as well as the signaling mechanisms in both isolated and tandem arrangements of PAS domains. This knowledge can be applied in engineering LOV-based photoswitches, opening up new design strategies and improving existing ones.