Comparative analysis of FKBP family protein: evaluation, structure, and function in mammals and Drosophila melanogaster.
Comparative analysis of FKBP family protein: evaluation, structure, and function in mammals and Drosophila melanogaster.
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FKBP 家族蛋白的比较分析：哺乳动物和果蝇中的评估、结构和功能
DOI：
10.1186/s12861-018-0167-3
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发表时间：
2018-03-27
影响因子：
--
通讯作者：
Xu X
中科院分区：
文献类型：
--
作者：
Ghartey-Kwansah G;Li Z;Feng R;Wang L;Zhou X;Chen FZ;Xu MM;Jones O;Mu Y;Chen S;Bryant J;Isaacs WB;Ma J;Xu X
fk506结合蛋白（fk506 binding proteins, FKBPs）已成为多个领域的研究热点，从而确定了FKBPs影响产前发育和许多人类疾病发病机制的几种细胞和分子途径。该分析揭示了哺乳动物和果蝇FKBPs机制在免疫抑制药物FK506和雷帕霉素作用下的差异。这些差异可以用来设计针对昆虫的杀虫剂。(1) FKBP家族蛋白的分子系统发育分析表明，已知的8个果蝇FKBPs与人类FKBP12具有同源性。这表明它们有密切的进化关系，可能来自一个共同的祖先。(2)已知的FKBPs含有FK结构域，即通过抑制钙调磷酸酶介导免疫抑制的脯氨酸顺/反式异构酶（PPIase）结构域。dFKBP59、CG4735/Shutdown、CG1847和CG5482在c端有一个四肽受体结构域，调控转录和蛋白转运。(3) FKBP51和FKBP52 （dFKBP59）与亲环蛋白40和蛋白磷酸酶5在类固醇受体-Hsp90异质复合物中作为Hsp90免疫亲和蛋白的共同伴侣。这些亲免疫蛋白在与正常生理相关的途径中是潜在的药物靶点，可以通过靶向胞外/内吞循环和囊泡运输来治疗各种类固醇性疾病。(4) FKBP14通过与Notch信号通路的关键组分presinilin结合，是Notch在细胞膜上激活的下游效应物。同时，Shutdown与piwi相互作用RNA通路中的转座子相关，在生殖细胞和卵巢体细胞中都起着至关重要的作用。dFKBPs的突变或沉默导致果蝇的早期胚胎死亡。因此，进一步了解FK506和雷帕霉素结合亲免疫蛋白FKBPs在哺乳动物和果蝇内分泌、心血管和神经功能中的作用机制，将为开发针对上述细胞信号通路的独特昆虫特异性治疗药物提供前景。结论本文综述了FKBP家族蛋白的功能作用，并系统总结了果蝇和哺乳动物FKBP蛋白的异同。针对细胞信号通路的特异性治疗也将被讨论。
BackgroundFK506-binding proteins (FKBPs) have become the subject of considerable interest in several fields, leading to the identification of several cellular and molecular pathways in which FKBPs impact prenatal development and pathogenesis of many human diseases.Main bodyThis analysis revealed differences between how mammalian and Drosophila FKBPs mechanisms function in relation to the immunosuppressant drugs, FK506 and rapamycin. Differences that could be used to design insect-specific pesticides. (1) Molecular phylogenetic analysis of FKBP family proteins revealed that the eight known Drosophila FKBPs share homology with the human FKBP12. This indicates a close evolutionary relationship, and possible origination from a common ancestor. (2) The known FKBPs contain FK domains, that is, a prolyl cis/trans isomerase (PPIase) domain that mediates immune suppression through inhibition of calcineurin. The dFKBP59, CG4735/Shutdown, CG1847, and CG5482 have a Tetratricopeptide receptor domain at the C-terminus, which regulates transcription and protein transportation. (3) FKBP51 and FKBP52 (dFKBP59), along with Cyclophilin 40 and protein phosphatase 5, function as Hsp90 immunophilin co-chaperones within steroid receptor-Hsp90 heterocomplexes. These immunophilins are potential drug targets in pathways associated with normal physiology and may be used to treat a variety of steroid-based diseases by targeting exocytic/endocytic cycling and vesicular trafficking. (4) By associating with presinilin, a critical component of the Notch signaling pathway, FKBP14 is a downstream effector of Notch activation at the membrane. Meanwhile, Shutdown associates with transposons in the PIWI-interacting RNA pathway, playing a crucial role in both germ cells and ovarian somas. Mutations in or silencing of dFKBPs lead to early embryonic lethality in Drosophila. Therefore, further understanding the mechanisms of FK506 and rapamycin binding to immunophilin FKBPs in endocrine, cardiovascular, and neurological function in both mammals and Drosophila would provide prospects in generating unique, insect specific therapeutics targeting the above cellular signaling pathways.ConclusionThis review will evaluate the functional roles of FKBP family proteins, and systematically summarize the similarities and differences between FKBP proteins in Drosophila and Mammals. Specific therapeutics targeting cellular signaling pathways will also be discussed.
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影响因子：
3.7
作者：
Dhamad AE;Zhou Z;Zhou J;Du Y
通讯作者：
Du Y
影响因子：
5.3
作者：
Ahn JC;Kim DW;You YN;Seok MS;Park JM;Hwang H;Kim BG;Luan S;Park HS;Cho HS
通讯作者：
Cho HS
影响因子：
5.7
作者：
Barbagallo B;Garrity PA
通讯作者：
Garrity PA
影响因子：
12.7
作者：
Dakson A;Yokota O;Esiri M;Bigio EH;Horan M;Pendleton N;Richardson A;Neary D;Snowden JS;Robinson A;Davidson YS;Mann DM
通讯作者：
Mann DM
影响因子：
7.1
作者：
Brai E;Alina Raio N;Alberi L
通讯作者：
Alberi L