Controlling Protein Activity and Degradation Using Blue Light.

Controlling Protein Activity and Degradation Using Blue Light.
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使用蓝光控制蛋白质活性和降解

DOI:
10.1007/978-1-4939-3512-3_5
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发表时间:
2016
影响因子:
--
通讯作者:
Taxis C
Taxis C
中科院分区:
--
文献类型:
--
作者:
Lutz AP;Renicke C;Taxis C

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蛋白质稳定性的调节是真核细胞中的一个基本过程,细胞周期进程、忠实的染色体分离或蛋白质质量控制。蛋白质稳定性的合成调节需要条件降解序列(降解决定子),其在特定信号下诱导稳定性转换。与选定的靶蛋白的融合允许影响细胞中的几乎每一个过程。光作为信号是有利的,因为它在时间、空间、质量和数量上的精确适用性。光调控蛋白质稳定性是通过将拟南芥亲光蛋白1的LOV 2光感受器结构域与合成的降解决定子(cODC 1)融合得到的光敏降解决定子(psd)模块来实现的。psd模块可以连接到定位于细胞溶胶或细胞核的靶蛋白的羧基末端,以获得对其稳定性的光控制。蓝光诱导LOV2结构域的结构变化,这反过来导致降解决定子的激活,从而导致整个融合蛋白的蛋白酶体降解。具有不同特性的psd模块变体可用于微调所选目标在允许(黑暗)和限制条件(蓝光)下的稳定性。
Regulation of protein stability is a fundamental process in eukaryotic cells and pivotal to, e.g., cell cycle progression, faithful chromosome segregation, or protein quality control. Synthetic regulation of protein stability requires conditional degradation sequences (degrons) that induce a stability switch upon a specific signal. Fusion to a selected target protein permits to influence virtually every process in a cell. Light as signal is advantageous due to its precise applicability in time, space, quality, and quantity. Light control of protein stability was achieved by fusing the LOV2 photoreceptor domain ofArabidopsis thalianaphototropin1 with a synthetic degron (cODC1) derived from the carboxy-terminal degron of ornithine decarboxylase to obtain the photosensitive degron (psd) module. The psd module can be attached to the carboxy terminus of target proteins that are localized to the cytosol or nucleus to obtain light control over their stability. Blue light induces structural changes in the LOV2 domain, which in turn lead to activation of the degron and thus proteasomal degradation of the whole fusion protein. Variants of the psd module with diverse characteristics are useful to fine-tune the stability of a selected target at permissive (darkness) and restrictive conditions (blue light).
DOI: 10.1073/pnas.81.15.4819
发表时间: 1984-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
YAFFE, MP;SCHATZ, G
通讯作者: SCHATZ, G
TIPI:TEV 蛋白酶介导的蛋白质不稳定诱导。
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DOI: 10.1016/j.chembiol.2013.03.005
发表时间: 2013-04-18
影响因子: --
作者:
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通讯作者: Taxis, Christof