Deg9的晶體結構揭示了一種新型的八聚體型HtrA蛋白酶

02-01

本文2017年11月27日在線發表於Nat ure Plants，原題目為：

The crystal structure of Deg9 reveals a novel octameric-type HtrA protease

摘要：

HtrA蛋白酶（也稱為Deg蛋白酶）通過調節蛋白質質量和數量在不同的生物體中起重要作用。16個擬南芥同源物中的一個，Deg9定位於細胞核，它通過降解ARR4來調節細胞分裂素和光介導的信號。為了揭示Deg9蛋白水解活性的結構特徵，我們確定了它的晶體結構。與HtrA建立的三元構建模塊不同，Deg9展示了由兩個具有不同構象的四聚體環組成的新八聚體結構。基於結構體系，我們構建了Deg9的幾種突變體，確定了它們的結構並測試了它們對ARR4的蛋白水解活性。結構和生物化學分析的結果使我們能夠建立Deg9底物識別和活性調控新機制的模型。在這個模型中，一個四聚體的蛋白酶激活通過蛋白酶結構域的整體重新定向來調節，以打開相反（無活性）四聚體中底物的入口。這項研究為了解植物蛋白酶如何調節核信號成分的水平提供了結構基礎。

Abstract

The high temperature requirement A (HtrA) proteases (also termed Deg proteases) play important roles in diverse organisms by regulating protein quality and quantity. One of the 16 Arabidopsis homologs, Deg9, is located in the nucleus where it modulates cytokinin- and light-mediated signalling via degrading the ARABIDOPSIS RESPONSE REGULATOR 4 (ARR4). To uncover the structural features underlying the proteolytic activity of Deg9, we determined its crystal structure. Unlike the well-established trimeric building block of HtrAs, Deg9 displays a novel octameric structure consisting of two tetrameric rings that have distinct conformations. Based on the structural architecture, we generated several mutant variants of Deg9, determined their structure and tested their proteolytic activity towards ARR4. The results of the structural and biochemical analyses allowed us to propose a model for a novel mechanism of substrate recognition and activity regulation of Deg9. In this model, protease activation of one tetramer is mediated by en-bloc reorientation of the protease domains to open an entrance for the substrate in the opposite (inactive) tetramer. This study provides the structural basis for understanding how the levels of nuclear signal components are regulated by a plant protease.

每日一詞

proteolytic

英[pr??t??l?t?k]

美[?pro?ti:?l?t?k]

adj.

（分）解蛋白的，蛋白水解的;

[例句]Proteolysis The hydrolysis of proteins into their amino acid. Enzymes that catalyze this are proteases or proteolytic enzymes.

蛋白質水解：指蛋白質被水解為氨基酸。催化的酶為蛋白酶或蛋白水解酶。