近期的Journal of Biological Chemistry上,清華大學(xué)醫(yī)學(xué)院教授,、生命學(xué)院兼職教授顏寧領(lǐng)導(dǎo)的研究組發(fā)表兩篇研究論文,系統(tǒng)闡述了ABA分子功能類似物Pyrabactin選擇性作用于脫落酸受體的分子機制,，為設(shè)計發(fā)展可施用于農(nóng)業(yè)的ABA替代小分子提供了分子基礎(chǔ),。這兩篇論文的電子版分別于6月16日和7月15日在線發(fā)表。
脫落酸（Abscisic acid, ABA）是植物中最為重要的激素之一,，它與植物生長發(fā)育和抗逆抗旱等生理過程都有極為密切的關(guān)系,。2009年4月，美國和歐洲的兩個研究組獨立發(fā)現(xiàn)了一類被命名為PYR1/PYL/RCAR的蛋白可能為ABA受體,。同年秋,，顏寧教授的研究組和美國、日本、歐洲的其他四個研究組分別利用結(jié)構(gòu)生物學(xué)和生物化學(xué)方法獨立證實了這類蛋白就是ABA受體,，并且揭示了其作用分子機制,。ABA受體的發(fā)現(xiàn)與結(jié)構(gòu)生物學(xué)鑒定被Science雜志評為2009年度十大突破之一。
Science評出2009年十大科學(xué)進(jìn)展
由于ABA在保護(hù)植物對抗逆境中的重要作用,，ABA在農(nóng)業(yè)中應(yīng)該有重要的應(yīng)用價值,。然而，由于ABA的不穩(wěn)定性以及合成ABA的高昂成本,，需要開發(fā)ABA的功能類似分子以實現(xiàn)農(nóng)業(yè)應(yīng)用的可能,。Pyrabactin是被報道的對PYL蛋白有選擇性的ABA類似物，但是pyrabacin的化學(xué)結(jié)構(gòu)與ABA十分不同,，其工作機制以及對PYL的選擇機理都不清楚,。顏寧教授的研究組在以前工作的基礎(chǔ)上又對小分子Pyrabactin對PYL蛋白的作用機制進(jìn)行了詳細(xì)研究。在第一篇JBC論文中,，研究小組解析了 Pyrabactin與受體PYL1的復(fù)合物結(jié)構(gòu),，通過與之前解析的ABA結(jié)合狀態(tài)下PYL1復(fù)合物結(jié)構(gòu)比較和生化實驗，總結(jié)出設(shè)計ABA類似物時重要功能基團(tuán)的組織規(guī)律,，這為設(shè)計ABA功能類似化學(xué)小分子并應(yīng)用于農(nóng)業(yè)生產(chǎn)提供了指導(dǎo)作用,。在第二篇論文中，研究小組揭示了Pyrabactin分子選擇性作用PYLs蛋白家族中幾個蛋白的分子機制,，他們得到Pyrabactin與受體PYL2的復(fù)合物結(jié)構(gòu),，他們發(fā)現(xiàn)，非常令人驚訝的是僅僅由于一個氨基酸的變化（VAL to ILE）引起了PYL蛋白對Pyrabactin產(chǎn)生了不同的結(jié)合方式,，從而決定了pyrabactin的選擇性。這項研究顯示了植物中PYL介導(dǎo)的 ABA受體通路調(diào)控的復(fù)雜性,。（生物谷Bioon.com）
圖片來源：清華大學(xué)生命科學(xué)學(xué)院網(wǎng)站
NSMB：脫落酸受體介導(dǎo)脫落酸信號傳導(dǎo)的分子機制
Cell：發(fā)現(xiàn)兩種新型脫落酸受體
Nature：脫落酸（ABA）的晶體結(jié)構(gòu)
Science：確認(rèn)新的ABA受體
Nature：蛋白質(zhì)PYR1調(diào)節(jié)植物抗旱機制
生物谷推薦英文摘要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.
生物谷推薦英文摘要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.
