Allosteric receptor activation by the plant peptide hormone phytosulfokine

Wang Jizong; Li Hongju; Han Zhifu; Zhang Heqiao; Wang Tong; Lin Guangzhong; Chang Junbiao; Yang Weicai; Chai Jijie

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Allosteric receptor activation by the plant peptide hormone phytosulfokine

机译：植物肽激素植物硫素激活别构受体

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Phytosulfokine (PSK) is a disulfated pentapeptide that has a ubiquitous role in plant growth and development(1,2). PSK is perceived by its receptor PSKR3,4, a leucine-rich repeat receptor kinase (LRR-RK). The mechanisms underlying the recognition of PSK, the activation of PSKR and the identity of the components downstream of the initial binding remain elusive. Here we report the crystal structures of the extracellular LRR domain of PSKR in free, PSK-and co-receptor-bound forms. The structures reveal that PSK interacts mainly with a b-strand from the island domain of PSKR, forming an anti-b-sheet. The two sulfate moieties of PSK interact directly with PSKR, sensitizing PSKR recognition of PSK. Supported by biochemical, structural and genetic evidence, PSK binding enhances PSKR heterodimerization with the somatic embryogenesis receptor-like kinases (SERKs). However, PSK is not directly involved in PSKR-SERK interaction but stabilizes PSKR island domain for recruitment of a SERK. Our data reveal the structural basis for PSKR recognition of PSK and allosteric activation of PSKR by PSK, opening up new avenues for the design of PSKR-specific small molecules.

机译：植物硫代植物因子（PSK）是一种二硫化五肽，在植物的生长和发育中起着普遍的作用（1,2）。 PSK的受体PSKR3,4是一种富含亮氨酸的重复受体激酶（LRR-RK）。 PSK的识别，PSKR的激活以及初始结合下游组分的身份所依据的机制仍然难以捉摸。在这里，我们以自由，PSK和共受体绑定形式报告PSKR的细胞外LRR域的晶体结构。这些结构表明，PSK主要与来自PSKR岛域的b链相互作用，形成抗b折叠。 PSK的两个硫酸根部分直接与PSKR相互作用，从而使PSKR对PSK的识别更加敏锐。在生化，结构和遗传证据的支持下，PSK结合可通过体细胞胚发生受体样激酶（SERK）增强PSKR异二聚化。但是，PSK并不直接参与PSKR-SERK相互作用，而是稳定PSKR岛域以招募SERK。我们的数据揭示了PSKR识别PSK和PSK变构激活PSKR的结构基础，为设计PSKR特异性小分子开辟了新途径。

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来源
《Nature》 |2015年第7568期|265-268|共4页
作者
Wang Jizong; Li Hongju; Han Zhifu; Zhang Heqiao; Wang Tong; Lin Guangzhong; Chang Junbiao; Yang Weicai; Chai Jijie;
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Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Ctr Struct Biol Sch Life Sci, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China;

Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China;

Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Ctr Struct Biol Sch Life Sci, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China;

Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Ctr Struct Biol Sch Life Sci, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China;

Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China;

Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Ctr Struct Biol Sch Life Sci, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China;

Zhengzhou Univ, Sch Chem & Mol Engn, Zhengzhou 450001, Peoples R China;

Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100101, Peoples R China;

Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Ctr Struct Biol Sch Life Sci, Minist Educ,Key Lab Prot Sci, Beijing 100084, Peoples R China;

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收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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1. Growth hormone secretagogues and growth hormone releasing peptides act as orthosteric super-agonists but not allosteric regulators for activation of the G protein Galpha(o1) by the Ghrelin receptor. [J] . Bennett KA, Langmead CJ, Wise A Molecular pharmacology. . 2009,第4期

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2. Anti-pathogenic properties of plant peptide hormone phytosulfokines (PSK's) and its selected analogues. [J] . Bahyrycz A., Saniewska A., Konopinska D. Pestycydy . 2008,第0期

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3. Further analogues of plant peptide hormone phytosulfokine-alpha (PSK-alpha) and their biological evaluation [J] . Bahyrycz A, Matsubayashi Y, Ogawa M, Journal of peptide science: An official publication of the European Peptide Society . 2005,第9期

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4. NOVEL BIOLOGICAL EFFECT OF PLANT PEPTIDE HORMONE PHYTOSULFOKINE-α (PSK-α) AND ITS SELECTED ANALOGUES [C] . Agata Bahyrycz, Monika Rykaczewska-Czerwinska, Andrzej Plech the European Peptide Symposium . 2007

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5. Activation of the parathyroid hormone/parathyroid hormone related peptide common receptor (PPR) modulates specific regional, temporal and signal transduction events in an avian sternal model. [D] . Harrington, Erik Kern. 2007

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6. Growth Hormone Secretagogues and Growth Hormone Releasing Peptides Act As Orthosteric Super-Agonists but Not Allosteric Regulators for Activation of the G Protein Gαo1 by the Ghrelin Receptor [O] . Kirstie A. Bennett, Christopher J. Langmead, Alan Wise, -1

机译：生长激素促分泌素和生长激素释放肽充当正构超激动剂但不是变构调节剂可通过Ghrelin受体激活G蛋白Gαo1。
7. Growth Hormone Secretagogues and Growth Hormone Releasing Peptides Act As Orthosteric Super-Agonists but Not Allosteric Regulators for Activation of the G Protein Gαo1 by the Ghrelin Receptor [O] . Bennett, Kirstie A., Langmead, Christopher J., Wise, Alan, 2009

机译：生长激素促分泌素和生长激素释放肽充当正构超激动剂，但不是变构调节剂，可通过Ghrelin受体激活G蛋白Gαo1。

Allosteric receptor activation by the plant peptide hormone phytosulfokine

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