Structure and Function of the PB1 Domain, a Protein Interaction Module Conserved in Animals, Fungi, Amoebas, and Plants
Structure and Function of the PB1 Domain, a Protein Interaction Module Conserved in Animals, Fungi, Amoebas, and Plants
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DOI：
10.1126/stke.4012007re6
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发表时间：
2007-08
期刊：
影响因子：
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通讯作者：
H. Sumimoto;S. Kamakura;Takashi Ito
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文献类型：
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作者：
H. Sumimoto;S. Kamakura;Takashi Ito
包含PB 1结构域的蛋白质是在动物、真菌、变形虫和植物中保守的蛋白质相互作用模块，参与多种生物过程。PB 1结构域采用泛素样β-抓取折叠，包含两个α螺旋和一个混合的五链β折叠，并分为具有酸性OPCA基序（I型）、第一个β链上的不变赖氨酸残基（II型）或两者（I/II型）的组。I型PB 1结构域的OPCA基序与II型PB 1结构域的碱性残基（特别是保守的赖氨酸）形成盐桥，从而介导特异性PB 1-PB 1异源二聚化，而额外的接触有助于模块相互作用的高亲和力和特异性。p40 phox和p67 phox之间形成复合物需要典型的PB 1二聚化（用于激活对哺乳动物宿主防御至关重要的NADPH氧化酶），在支架Bem 1和鸟嘌呤核苷酸交换因子Cdc 24之间（用于酵母中的极性建立），以及极性蛋白Par 6和非典型蛋白激酶C之间（用于动物细胞中的细胞极化），以及丝裂原活化蛋白激酶MEKK 2或MEKK 3与下游靶丝裂原活化蛋白激酶激酶MEK 5之间的相互作用（用于哺乳动物中的早期心血管发育）。PB 1结构域也可以介导与其他蛋白质结构域的相互作用。例如，p40 phox的PB 1和PX结构域之间的分子内相互作用调节杀微生物NADPH氧化酶的吞噬体靶向; MEK 5的PB 1结构域可能负责结合下游激酶ERK 5，其缺乏PB 1结构域;支架蛋白Nbr 1通过含有PB 1的区域与肌联蛋白（一种没有PB 1结构域的肌节蛋白）结合。本文综述了PB 1结构域在分子和细胞水平的各个方面。本文通过9幅图、4幅交互结构图和170篇引文，描述了PB 1结构域蛋白质的结构与功能关系。存在三种类型的含有PB 1的蛋白质：具有I型结构域的那些，具有II型结构域的那些，以及具有I型和II型（I/II型）的那些。I型结构域介导与含有典型PB 1-PB 1相互作用中的II型结构域的蛋白质的相互作用。由PB 1结构域介导的相互作用对于组织细胞结构是重要的，例如，在极化细胞（上皮细胞和神经元）和骨骼肌中。此外，涉及PB 1结构域的相互作用影响促分裂原活化蛋白激酶信号传导的活化和NADPH氧化酶的活化。
Proteins containing the PB1 domain, a protein interaction module conserved in animals, fungi, amoebas, and plants, participate in diverse biological processes. The PB1 domains adopt a ubiquitin-like β-grasp fold, containing two α helices and a mixed five-stranded β sheet, and are classified into groups harboring an acidic OPCA motif (type I), the invariant lysine residue on the first β strand (type II), or both (type I/II). The OPCA motif of a type I PB1 domain forms salt bridges with basic residues, especially the conserved lysine, of a type II PB1 domain, thereby mediating a specific PB1-PB1 heterodimerization, whereas additional contacts contribute to high affinity and specificity of the modular interaction. The canonical PB1 dimerization is required for the formation of complexes between p40phox and p67phox (for activation of the NADPH oxidase crucial for mammalian host defense), between the scaffold Bem1 and the guanine nucleotide exchange factor Cdc24 (for polarity establishment in yeasts), and between the polarity protein Par6 and atypical protein kinase C (for cell polarization in animal cells), as well as for the interaction between the mitogen-activated protein kinase kinase kinases MEKK2 or MEKK3 and the downstream target mitogen-activated protein kinase kinase MEK5 (for early cardiovascular development in mammals). PB1 domains can also mediate interactions with other protein domains. For example, an intramolecular interaction between the PB1 and PX domains of p40phox regulates phagosomal targeting of the microbicidal NADPH oxidase; the PB1 domain of MEK5 is likely responsible for binding to the downstream kinase ERK5, which lacks a PB1 domain; and the scaffold protein Nbr1 associates through a PB1-containing region with titin, a sarcomere protein without a PB1 domain. This Review describes various aspects of PB1 domains at the molecular and cellular levels. With 9 figures, four interactive structure figures, and 170 citations, this Review describes the structure-function relationships of proteins with PB1 domains. Three types of PB1-containing proteins occur: those with a type I domain, those with a type II domain, and those with both type I and type II (type I/II). The type I domain mediates interactions with proteins containing a type II domain in a canonical PB1-PB1 interaction. Interactions mediated by PB1 domains are important for organizing cell structure, for example, in polarized cells (epithelial cells and neurons) and in skeletal muscle. In addition, interactions involving PB1 domains influence the activation of mitogen-activated protein kinase signaling and activation of NADPH oxidase.