The velvet family of fungal regulators contains a DNA-binding domain structurally similar to NF-κB.
The velvet family of fungal regulators contains a DNA-binding domain structurally similar to NF-κB.
复制标题
DOI：
10.1371/journal.pbio.1001750
复制
发表时间：
2013-12
期刊：
影响因子：
9.8
通讯作者：
Ficner R
中科院分区：
文献类型：
--
作者：
Ahmed YL;Gerke J;Park HS;Bayram Ö;Neumann P;Ni M;Dickmanns A;Kim SC;Yu JH;Braus GH;Ficner R
这项研究揭示了一个重要的真菌调节蛋白家族是转录因子，其包含结构上与哺乳动物NF κ B相关的DNA结合“天鹅绒”结构域。真菌的形态发育和次生代谢产物的合成具有防御和保护作用。这些过程主要是协调天鹅绒监管机构，其中包含一个功能和结构不明天鹅绒域。在这里，我们证明了VosA的天鹅绒结构域是一种新的DNA结合基序，它特异性地识别由关键发育调控基因的启动子中的两个基序组成的11个核苷酸的共有序列。VosA天鹅绒结构域的晶体结构分析揭示了与哺乳动物转录因子NF-κB的Rel同源结构域（RHD）的不可预见的结构相似性。基于这种结构相似性，已经鉴定了存在于所有天鹅绒结构域中的几个保守氨基酸残基，并显示其对于VosA的DNA结合能力是必需的。天鹅绒结构域也参与二聚体形成，如在VosA同源二聚体和VosA-VelB异源二聚体的溶解晶体结构中所见。这些发现表明，真菌和动物的防御机制可能是由结构相关的DNA结合转录因子。在许多真菌中，发育过程和非必需化学物质（次级代谢产物）的合成受到各种外部刺激（如光）的调节。尽管真菌将它们用于防御目的，但次级代谢产物的范围从有用的抗生素到强大的毒素，因此了解调节其合成的分子过程对我们特别感兴趣。在构巢曲霉中，这些过程的主要调节因子是所谓的“天鹅绒”蛋白VeA、VelB和VosA，它们共有一个150个氨基酸的区域，称为天鹅绒结构域。天鹅绒蛋白相互作用，单独（“同源二聚体”），在各种组合（“异源二聚体”），也与其他蛋白质，但这些蛋白质发挥其调节功能的分子机制尚不清楚。在这项工作中，我们表明，天鹅绒蛋白形成一个家庭的真菌特异性转录因子，直接结合到目标DNA，即使他们的氨基酸序列分析没有发现任何已知的DNA结合域或图案。我们确定了VosA-VosA同源二聚体和VosA-VelB异源二聚体的三维结构，发现尽管序列相似性非常低，但天鹅绒结构域的结构强烈地让人联想到哺乳动物转录因子NFκB-p50中的N-末端免疫球蛋白样结构域。我们认为，与NFκB一样，天鹅绒蛋白的各种同源或异源二聚体调节基因表达，以驱动真菌的发育和防御途径。
This study reveals an important family of fungal regulatory proteins to be transcription factors that contain a DNA-binding “velvet” domain structurally related to that of mammalian NFkB. Morphological development of fungi and their combined production of secondary metabolites are both acting in defence and protection. These processes are mainly coordinated by velvet regulators, which contain a yet functionally and structurally uncharacterized velvet domain. Here we demonstrate that the velvet domain of VosA is a novel DNA-binding motif that specifically recognizes an 11-nucleotide consensus sequence consisting of two motifs in the promoters of key developmental regulatory genes. The crystal structure analysis of the VosA velvet domain revealed an unforeseen structural similarity with the Rel homology domain (RHD) of the mammalian transcription factor NF-κB. Based on this structural similarity several conserved amino acid residues present in all velvet domains have been identified and shown to be essential for the DNA binding ability of VosA. The velvet domain is also involved in dimer formation as seen in the solved crystal structures of the VosA homodimer and the VosA-VelB heterodimer. These findings suggest that defence mechanisms of both fungi and animals might be governed by structurally related DNA-binding transcription factors. In many fungi, developmental processes and the synthesis of nonessential chemicals (secondary metabolites) are regulated by various external stimuli, such as light. Although fungi employ them for defensive purposes, secondary metabolites range from useful antibiotics to powerful toxins, so understanding the molecular processes that regulate their synthesis is of particular interest to us. In the mold Aspergillus nidulans the main regulators of these processes are the so-called “velvet” proteins VeA, VelB, and VosA, which share a 150-amino acid region known as the velvet domain. Velvet proteins interact with each other, alone (“homodimers”), in various combinations (“heterodimers”), and also with other proteins, but the molecular mechanism by which these proteins exert their regulatory function has been unclear. In this work we show that velvet proteins form a family of fungus-specific transcription factors that directly bind to target DNA, even though analysis of their amino acid sequence does not reveal any known DNA-binding domains or motifs. We determined the three-dimensional structure of the VosA-VosA homodimer and the VosA-VelB heterodimer and found that the structure of the velvet domain is strongly reminiscent of the N-terminal immunoglobulin-like domain found in the mammalian transcription factor NFκB-p50, despite the very low sequence similarity. We propose that, like NFκB, various homo- or heterodimers of velvet proteins modulate gene expression to drive development and defensive pathways in fungi.
登录
查看更多内容
影响因子：
--
作者：
Dhingra, Sourabh;Andes, David;Calvo, Ana M.
通讯作者：
Calvo, Ana M.
影响因子：
3.6
作者：
Han, KH;Seo, JA;Yu, JH
通讯作者：
Yu, JH
影响因子：
64.5
作者：
Huxford, T;Huang, DB;Ghosh, G
通讯作者：
Ghosh, G
影响因子：
64.8
作者：
GHOSH, G;VANDUYNE, G;SIGLER, PB
通讯作者：
SIGLER, PB
DOI：
10.1073/pnas.90.24.11558
发表时间：
1993-12-15
影响因子：
11.1
作者：
BALDAUF, SL;PALMER, JD
通讯作者：
PALMER, JD