Crystal structure and interaction studies of the human FBxo3 ApaG domain.
Crystal structure and interaction studies of the human FBxo3 ApaG domain.
复制标题
DOI：
10.1111/febs.13721
复制
发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Gronenborn AM
中科院分区：
文献类型：
--
作者：
Krzysiak TC;Chen BB;Lear T;Mallampalli RK;Gronenborn AM
促炎细胞因子的转录激活，由肿瘤坏死因子受体相关因子（TRAFs）介导，部分是由F-box蛋白FBxl2通过含有另一个F-box蛋白FBxo3的E3连接酶降解触发的。FBxo3的ApaG结构域与FBxl2相互作用和降解的关系[J].中国生物医学工程学报，2013,29(2):557 - 557。在这里，我们报告了人类FBxo3 ApaG结构域的x射线结构，残基278-407,2.0 Å分辨率。与细菌ApaG蛋白一样，该结构域的特征是典型的免疫球蛋白/纤维连接蛋白iii型折叠，包括一个七链β-片核心，周围环绕着四个扩展环。虽然已经提出了细菌ApaG蛋白的阳离子结合，但在人类ApaG结构域未检测到与Mg2+或Co2+的相互作用。此外，二核苷酸多磷酸，已被报道为炎症反应中的第二信使和细菌含ApaG操纵子的靶标，不受人类ApaG结构域的结合。在全长蛋白的背景下，环1包含294-303残基，是与FBxl2相互作用的关键。然而，用一个在关键T404上磷酸化的15-mer FBxl2肽对单个ApaG结构域进行滴定，以及通过共免疫沉淀评估ApaG结构域无法与全长FBxl2相互作用，表明ApaG结构域单独是必要的，但不足以结合和降解FBxl2。
Transcriptional activation of proinflammatory cytokines, mediated by tumor necrosis factor receptor-associated factors (TRAFs), is in part triggered by the degradation of the F-box protein, FBxl2, via an E3 ligase that contains another F-box protein, FBxo3. The ApaG domain of FBxo3 is required for the interaction with and degradation of FBxl2 [Mallampalli RK et al., (2013) J Immunol 191, 5247–5255]. Here, we report the X-ray structure of the human FBxo3 ApaG domain, residues 278–407, at 2.0 Å resolution. Like bacterial ApaG proteins, this domain is characterized by a classic Immunoglobin/Fibronectin III-type fold, comprising a seven-stranded β-sheet core, surrounded by four extended loops. Although cation binding had been proposed for bacterial ApaG proteins, no interactions with Mg2+ or Co2+ were detected for the human ApaG domain. In addition, dinucleotide polyphosphates, which have been reported to be second messengers in the inflammation response and targets of the bacterial apaG-containing operon, are not bound by the human ApaG domain. In the context of the full-length protein, loop 1, comprising residues 294–303, is critical for the interaction with FBxl2. However, titration of the individual ApaG domain with a 15-mer FBxl2 peptide that was phosphorylated on the crucial T404, as well as the inability of the ApaG domain to interact with full-length FBxl2, assessed by coimmunoprecipitation, indicate that the ApaG domain alone is necessary, but not sufficient for binding and degradation of FBxl2.
登录
查看更多内容
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
3.6
作者：
GIBSON, MM;BAGGA, DA;MAGUIRE, ME
通讯作者：
MAGUIRE, ME
影响因子：
4.8
作者：
Liu, L;Rodriguez-Bèlmonte, EM;Lee, MYWT
通讯作者：
Lee, MYWT
影响因子：
14.9
作者：
Aravind, L;Koonin, EV
通讯作者：
Koonin, EV
影响因子：
64.8
作者：
SOMERS, W;ULTSCH, M;KOSSIAKOFF, AA
通讯作者：
KOSSIAKOFF, AA