徐华强 朱健康《Nature》ABA受体研究新进展

　　

生物通报道，美国Van Andel研究所结构科学部实验室H. Eric Xu（徐华强）教授，加州大学植物遗传生态学系朱健康教授联手在最新的Nature 在线版上（11月6日）发表ABA受体研究新成果文章A gate–latch–lock mechanism for hormone signalling by abscisic acid receptors。

 

参与研究的还包括中科院遗传与发育生物学研究所的李家洋院士，文章通讯作者是美国Van Andel研究所结构科学部实验室H. Eric Xu（徐华强）教授。

 

脱落酸（Abscisic acid, ABA）是植物中最为重要的激素之一，它与种子休眠、根系发育、叶子枯萎、抗旱反应和其它的生理过程都有极为密切的关系。由于脱落酸能引发的下游反应过多，包括激酶、磷酸酶、G蛋白、泛素通路中的蛋白等等都参与了ABA信号的调控，因此从ABA被发现半个世纪以来一直不清楚ABA的受体是什么。

 

过去几年陆续有一些关于ABA受体的发现报导，但其具体功能尚有所争议。今年四月底，Science发表两个独立研究组的最新成果，发现一类被命名为PYR/PYL或是RCAR的蛋白为ABA受体。这类蛋白可以在体内外结合ABA，之后会结合下游的蛋白磷酸酶PP2C并抑制其磷酸酶活性，然而其中的分子机制尚不清楚。并且由于之前关于ABA受体的诸多争议，PYL蛋白是否为真正的ABA受体也还有待进一步验证。在这种背景下，结构生物学研究变得至关重要。

 

徐华强教授等通过结构比较和生化分析，确认了PYL2–ABA–PP2C复合物的晶体结构，以及分析了该复合物对ABA信号通路的启动和关闭的分子结构机制。

 

有趣的是，这一研究领域的竞争异常激烈，而几个顶尖杂志的反应也是前所未有的迅速，从投稿到发表基本都在一个月左右。10月22日、23日，来自日本和美国的两个结构生物学研究组在Science和Nature分别以Research article和Article的形式online报道了上述三个结构中的部分研究11月5日，《Nature Structural & Molecular Biology》在线发表了清华大学颜宁等人发表的类似研究成果。而11月8日来自法国的研究组则以Nature Letter的形式报道了上述中的两个结构。

 

H. Eric Xu （徐华强）美国Van Andel研究所结构科学部实验室负责人，杰出PI（研究组长）。《核受体信号》、《分子内分泌学》编委，美国化学协会、分子内分泌学协会会员，VARI蛋白质组学与质谱监督委员会主席，获得GSK杰出研究奖。国内多家著名大学和科研机构正在积极争取H. Eric Xu教授来中国开展研究工作。

 

（生物通 小茜）

生物通推荐原文检索

Nature advance online publication 6 November 2009 | doi:10.1038/nature08613; Received 16 October 2009; Accepted 27 October 2009; Published online 6 November 2009

 

A gate–latch–lock mechanism for hormone signalling by abscisic acid receptors

 

Karsten Melcher1,7, Ley-Moy Ng1,2,7, X. Edward Zhou1,7, Fen-Fen Soon1,2,7, Yong Xu1, Kelly M. Suino-Powell1, Sang-Youl Park4, Joshua J. Weiner6, Hiroaki Fujii4,5, Viswanathan Chinnusamy4,5, Amanda Kovach1, Jun Li1,2, Yonghong Wang3, Jiayang Li3, Francis C. Peterson6, Davin R. Jensen6, Eu-Leong Yong2, Brian F. Volkman6, Sean R. Cutler4, Jian-Kang Zhu4,5 & H. Eric Xu1

 

Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue, N.E., Grand Rapids, Michigan 49503, USA

Department of Obstetrics & Gynecology, National University Hospital, Yong Loo Lin School of Medicine, Graduate School for Integrative Sciences & Engineering, National University of Singapore, Singapore 119074, Republic of Singapore

State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, National Center for Plant Gene Research, Beijing 100101, China

Department of Botany and Plant Sciences, University of California at Riverside, Riverside, California 92521, USA

Center for Plant Stress Genomics and Technology, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia

Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA

These authors contributed equally to this work.

Correspondence to: H. Eric Xu1 Correspondence and requests for materials should be addressed to H.E.X. (Email: [e-mail]).

【Abstract】

Abscisic acid (ABA) is a ubiquitous hormone that regulates plant growth, development and responses to environmental stresses. Its action is mediated by the PYR/PYL/RCAR family of START proteins, but it remains unclear how these receptors bind ABA and, in turn, how hormone binding leads to inhibition of the downstream type 2C protein phosphatase (PP2C) effectors. Here we report crystal structures of apo and ABA-bound receptors as well as a ternary PYL2–ABA–PP2C complex. The apo receptors contain an open ligand-binding pocket flanked by a gate that closes in response to ABA by way of conformational changes in two highly conserved -loops that serve as a gate and latch. Moreover, ABA-induced closure of the gate creates a surface that enables the receptor to dock into and competitively inhibit the PP2C active site. A conserved tryptophan in the PP2C inserts directly between the gate and latch, which functions to further lock the receptor in a closed conformation. Together, our results identify a conserved gate–latch–lock mechanism underlying ABA signalling.