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JBC:揭示脱落酸替代小分子的功能及选择性机理

来源:清华大学生命科学学院 2010-09-13 17:36

近期的Journal of Biological Chemistry上,清华大学医学院教授、生命学院兼职教授颜宁领导的研究组发表两篇研究论文,系统阐述了ABA分子功能类似物Pyrabactin选择性作用于脱落酸受体的分子机制,为设计发展可施用于农业的ABA替代小分子提供了分子基础。这两篇论文的电子版分别于6月16日和7月15日在线发表。

脱落酸(Abscisic acid, ABA)是植物中最为重要的激素之一,它与植物生长发育和抗逆抗旱等生理过程都有极为密切的关系。2009年4月,美国和欧洲的两个研究组独立发现了一类被命名为PYR1/PYL/RCAR的蛋白可能为ABA受体。同年秋,颜宁教授的研究组和美国、日本、欧洲的其他四个研究组分别利用结构生物学和生物化学方法独立证实了这类蛋白就是ABA受体,并且揭示了其作用分子机制。ABA受体的发现与结构生物学鉴定被Science杂志评为2009年度十大突破之一。

Science评出2009年十大科学进展

由于ABA在保护植物对抗逆境中的重要作用,ABA在农业中应该有重要的应用价值。然而,由于ABA的不稳定性以及合成ABA的高昂成本,需要开发ABA的功能类似分子以实现农业应用的可能。Pyrabactin是被报道的对PYL蛋白有选择性的ABA类似物,但是pyrabacin的化学结构与ABA十分不同,其工作机制以及对PYL的选择机理都不清楚。颜宁教授的研究组在以前工作的基础上又对小分子Pyrabactin对PYL蛋白的作用机制进行了详细研究。在第一篇JBC论文中,研究小组解析了 Pyrabactin与受体PYL1的复合物结构,通过与之前解析的ABA结合状态下PYL1复合物结构比较和生化实验,总结出设计ABA类似物时重要功能基团的组织规律,这为设计ABA功能类似化学小分子并应用于农业生产提供了指导作用。在第二篇论文中,研究小组揭示了Pyrabactin分子选择性作用PYLs蛋白家族中几个蛋白的分子机制,他们得到Pyrabactin与受体PYL2的复合物结构,他们发现,非常令人惊讶的是仅仅由于一个氨基酸的变化(VAL to ILE)引起了PYL蛋白对Pyrabactin产生了不同的结合方式,从而决定了pyrabactin的选择性。这项研究显示了植物中PYL介导的 ABA受体通路调控的复杂性。(生物谷Bioon.com)


图片来源:清华大学生命科学学院网站

NSMB:脱落酸受体介导脱落酸信号传导的分子机制
Cell:发现两种新型脱落酸受体
Nature:脱落酸(ABA)的晶体结构
Science:确认新的ABA受体
Nature:蛋白质PYR1调节植物抗旱机制

生物谷推荐英文摘要1:

JBC doi: 10.1074/jbc.M110.149005

Functional Mechanism of the Abscisic Acid Agonist Pyrabactin*
Qi Hao?§,1, Ping Yin?§,1, Chuangye Yan??,1, Xiaoqiu Yuan?§, Wenqi Li?§, Zhiping Zhang‖, Lei Liu‖, Jiawei Wang?? and Nieng Yan?§,2

From the ?State Key Laboratory of Biomembrane and Membrane Biotechnology,
§Center for Structural Biology, School of Medicine,
?School of Life Sciences, and
‖Department of Chemistry, Tsinghua University, Beijing 100084, China

Pyrabactin is a synthetic abscisic acid (ABA) agonist that selectively inhibits seed germination. The use of pyrabactin was pivotal in the identification of the PYR1/PYL/RCAR family (PYL) of proteins as the ABA receptor. Although they both act through PYL proteins, pyrabactin and ABA share no apparent chemical or structural similarity. It remains unclear how pyrabactin functions as an ABA agonist. Here, we report the crystal structure of pyrabactin in complex with PYL1 at 2.4 ? resolution. Structural and biochemical analyses revealed that recognition of pyrabactin by the pocket residues precedes the closure of switch loop CL2. Structural comparison between pyrabactin- and ABA-bound PYL1 reveals a general principle in the arrangements of function groups of the two distinct ligands. The study provides a framework for the development of novel ABA agonists that may have applicable potentials in agriculture.

生物谷推荐英文摘要2:

JBC doi: 10.1074/jbc.M110.160192

Single Amino Acid Alteration between Valine and Isoleucine Determines the Distinct Pyrabactin Selectivity by PYL1 and PYL2*
Xiaoqiu Yuan1, Ping Yin1, Qi Hao1, Chuangye Yan, Jiawei Wang and Nieng Yan2

From the State Key Laboratory of Biomembrane and Membrane Biotechnology, Center for Structural Biology, School of Medicine and School of Life Sciences, Tsinghua University, Beijing 100084, China

Abscisic acid (ABA) is one of the most important phytohormones in plant. PYL proteins were identified to be ABA receptors in Arabidopsis thaliana. Despite the remarkably high degree of sequence similarity, PYL1 and PYL2 exhibit distinct responses toward pyrabactin, an ABA agonist. PYL1 inhibits protein phosphatase type 2C upon binding of pyrabactin. In contrast, PYL2 appears relatively insensitive to this compound. The crystal structure of pyrabactin-bound PYL1 revealed that most of the PYL1 residues involved in pyrabactin binding are conserved, hence failing to explain the selectivity of pyrabactin for PYL1 over PYL2. To understand the molecular basis of pyrabactin selectivity, we determined the crystal structure of PYL2 in complex with pyrabactin at 1.64 ? resolution. Structural comparison and biochemical analyses demonstrated that one single amino acid alteration between a corresponding valine and isoleucine determines the distinct pyrabactin selectivity by PYL1 and PYL2. These characterizations provide an important clue to dissecting the redundancy of PYL proteins.

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