人类Naked2的结构研究：一种具有生物活性的内在无序蛋白质。
Structural studies of human Naked2: a biologically active intrinsically unstructured protein.
作者信息
Hu Tianhui, Krezel Andrzej M, Li Cunxi, Coffey Robert J
机构信息
Department of Medicine and Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
出版信息
Biochem Biophys Res Commun. 2006 Dec 1;350(4):911-5. doi: 10.1016/j.bbrc.2006.09.121. Epub 2006 Oct 2.
Abstract
Naked1 and 2 are two mammalian orthologs of Naked Cuticle, a canonical Wnt signaling antagonist in Drosophila. Naked2, but not Naked1, interacts with transforming growth factor-alpha (TGFalpha) and escorts TGFalpha-containing vesicles to the basolateral membrane of polarized epithelial cells. Full-length Naked2 is poorly soluble. Since most functional domains, including the Dishevelled binding region, EF-hand, vesicle recognition, and membrane targeting motifs, reside in the N-terminal half of the protein, we expressed and purified the first 217 residues of human Naked2 and performed a functional analysis of this fragment. Its circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra showed no evidence of secondary and/or tertiary structure. The fragment did not bind calcium or zinc. These results indicate that the N-terminal half of Naked2 behaves as an intrinsically unstructured protein.
摘要
Naked1和Naked2是果蝇中经典Wnt信号拮抗剂Naked Cuticle的两个哺乳动物直系同源物。Naked2而非Naked1与转化生长因子α（TGFα）相互作用，并将含TGFα的囊泡转运至极化上皮细胞的基底外侧膜。全长Naked2溶解性很差。由于大多数功能结构域，包括Dishevelled结合区域、EF手型结构、囊泡识别和膜靶向基序，都位于该蛋白质的N端一半区域，我们表达并纯化了人Naked2的前217个残基，并对该片段进行了功能分析。其圆二色性（CD）和核磁共振（NMR）光谱未显示二级和/或三级结构的证据。该片段不结合钙或锌。这些结果表明，Naked2的N端一半区域表现为一种内在无序蛋白。
相似文献
1
Structural studies of human Naked2: a biologically active intrinsically unstructured protein.人类Naked2的结构研究：一种具有生物活性的内在无序蛋白质。
Biochem Biophys Res Commun. 2006 Dec 1;350(4):911-5. doi: 10.1016/j.bbrc.2006.09.121. Epub 2006 Oct 2.
2
EGF receptor-independent action of TGF-alpha protects Naked2 from AO7-mediated ubiquitylation and proteasomal degradation.转化生长因子α（TGF-α）的表皮生长因子（EGF）受体非依赖性作用保护Naked2免受AO7介导的泛素化和蛋白酶体降解。
Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13433-8. doi: 10.1073/pnas.0806298105. Epub 2008 Aug 29.
3
Naked2 acts as a cargo recognition and targeting protein to ensure proper delivery and fusion of TGF-alpha containing exocytic vesicles at the lower lateral membrane of polarized MDCK cells.Naked2作为一种货物识别和靶向蛋白，以确保含转化生长因子α的分泌小泡在极化的MDCK细胞的下外侧膜处正确递送和融合。
Mol Biol Cell. 2007 Aug;18(8):3081-93. doi: 10.1091/mbc.e07-02-0172. Epub 2007 Jun 6.
4
Myristoylated Naked2 escorts transforming growth factor alpha to the basolateral plasma membrane of polarized epithelial cells.豆蔻酰化的Naked2将转化生长因子α转运至极化上皮细胞的基底外侧质膜。
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5571-6. doi: 10.1073/pnas.0401294101. Epub 2004 Apr 2.
5
Use of fluorescence-activated vesicle sorting for isolation of Naked2-associated, basolaterally targeted exocytic vesicles for proteomics analysis.利用荧光激活囊泡分选技术分离与Naked2相关的、靶向基底外侧的胞吐囊泡用于蛋白质组学分析。
Mol Cell Proteomics. 2008 Sep;7(9):1651-67. doi: 10.1074/mcp.M700155-MCP200. Epub 2008 May 25.
6
Polyglutamine tract binding protein-1 is an intrinsically unstructured protein.聚谷氨酰胺链结合蛋白-1是一种内在无序蛋白。
Biochim Biophys Acta. 2009 Jun;1794(6):936-43. doi: 10.1016/j.bbapap.2009.03.001. Epub 2009 Mar 17.
7
Structural studies on the Ca2+-binding domain of human nucleobindin (calnuc).人核结合蛋白（钙结合蛋白）钙结合结构域的结构研究。
Biochemistry. 2004 Aug 10;43(31):10039-49. doi: 10.1021/bi049310a.
8
Primary contact sites in intrinsically unstructured proteins: the case of calpastatin and microtubule-associated protein 2.内在无序蛋白质中的主要接触位点：以钙蛋白酶抑制蛋白和微管相关蛋白2为例。
Biochemistry. 2005 Mar 15;44(10):3955-64. doi: 10.1021/bi047817f.
9
Solution structure of the N-terminal zinc fingers of the Xenopus laevis double-stranded RNA-binding protein ZFa.非洲爪蟾双链RNA结合蛋白ZFa的N端锌指结构的溶液结构
J Mol Biol. 2005 Aug 26;351(4):718-30. doi: 10.1016/j.jmb.2005.06.032.
10
Structure and tropomyosin binding properties of the N-terminal capping domain of tropomodulin 1.原肌球蛋白调节蛋白1 N端封端结构域的结构及与原肌球蛋白的结合特性
Biophys J. 2005 Jan;88(1):372-83. doi: 10.1529/biophysj.104.051128. Epub 2004 Oct 8.
引用本文的文献
1
NKD2 is correlated with the occurrence, progression and prognosis of thyroid carcinoma.NKD2 与甲状腺癌的发生、进展和预后相关。
Eur J Med Res. 2022 Nov 8;27(1):235. doi: 10.1186/s40001-022-00853-2.
2
Epigenetic dysregulation of is a valuable predictor assessing treatment outcome in acute myeloid leukemia.表观遗传失调是评估急性髓系白血病治疗结果的一个有价值的预测指标。 （你提供的原文“Epigenetic dysregulation of ”表述不完整，这里是根据推测补充完整后翻译的。）
J Cancer. 2017 Feb 11;8(3):460-468. doi: 10.7150/jca.16914. eCollection 2017.
3
Silencing NKD2 by promoter region hypermethylation promotes gastric cancer invasion and metastasis by up-regulating SOX18 in human gastric cancer.启动子区域高甲基化沉默NKD2通过上调SOX18促进人胃癌的侵袭和转移。
Oncotarget. 2015 Oct 20;6(32):33470-85. doi: 10.18632/oncotarget.5272.
4
Epigenetic silencing of NKD2, a major component of Wnt signaling, promotes breast cancer growth.NKD2（Wnt信号的主要成分）的表观遗传沉默促进乳腺癌生长。
Oncotarget. 2015 Sep 8;6(26):22126-38. doi: 10.18632/oncotarget.4244.
5
A monoclonal antibody produced against Naked2.一种针对Naked2产生的单克隆抗体。
Monoclon Antib Immunodiagn Immunother. 2013 Aug;32(4):290-4. doi: 10.1089/mab.2012.0111.
6
Zebrafish Nkd1 promotes Dvl degradation and is required for left-right patterning.斑马鱼 Nkd1 促进 Dvl 降解，是左右图案形成所必需的。
Dev Biol. 2010 Dec 1;348(1):22-33. doi: 10.1016/j.ydbio.2010.08.040. Epub 2010 Sep 19.
7
Convergence between Wnt-β-catenin and EGFR signaling in cancer.Wnt-β-catenin 和 EGFR 信号通路在癌症中的交汇。
Mol Cancer. 2010 Sep 9;9:236. doi: 10.1186/1476-4598-9-236.
8
EGF receptor-independent action of TGF-alpha protects Naked2 from AO7-mediated ubiquitylation and proteasomal degradation.转化生长因子α（TGF-α）的表皮生长因子（EGF）受体非依赖性作用保护Naked2免受AO7介导的泛素化和蛋白酶体降解。
Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13433-8. doi: 10.1073/pnas.0806298105. Epub 2008 Aug 29.
本文引用的文献
1
PR130 is a modulator of the Wnt-signaling cascade that counters repression of the antagonist Naked cuticle.PR130是Wnt信号级联的一种调节剂，可对抗拮抗剂Naked cuticle的抑制作用。
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5397-402. doi: 10.1073/pnas.0507237103. Epub 2006 Mar 27.
2
Wnt signalling in stem cells and cancer.干细胞与癌症中的Wnt信号传导
Nature. 2005 Apr 14;434(7035):843-50. doi: 10.1038/nature03319.
3
PR72, a novel regulator of Wnt signaling required for Naked cuticle function.PR72，一种Naked表皮功能所需的Wnt信号通路新型调节因子。
Genes Dev. 2005 Feb 1;19(3):376-86. doi: 10.1101/gad.328905.
4
A targeted mutation of Nkd1 impairs mouse spermatogenesis.
J Biol Chem. 2005 Jan 28;280(4):2831-9. doi: 10.1074/jbc.M405680200. Epub 2004 Nov 16.
5
The role of structural disorder in the function of RNA and protein chaperones.结构紊乱在RNA和蛋白质伴侣功能中的作用。
FASEB J. 2004 Aug;18(11):1169-75. doi: 10.1096/fj.04-1584rev.
6
Myristoylated Naked2 escorts transforming growth factor alpha to the basolateral plasma membrane of polarized epithelial cells.豆蔻酰化的Naked2将转化生长因子α转运至极化上皮细胞的基底外侧质膜。
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5571-6. doi: 10.1073/pnas.0401294101. Epub 2004 Apr 2.
7
p27 binds cyclin-CDK complexes through a sequential mechanism involving binding-induced protein folding.p27通过一种涉及结合诱导蛋白质折叠的顺序机制与细胞周期蛋白 - 细胞周期蛋白依赖性激酶复合物结合。
Nat Struct Mol Biol. 2004 Apr;11(4):358-64. doi: 10.1038/nsmb746. Epub 2004 Mar 14.
8
Prediction and functional analysis of native disorder in proteins from the three kingdoms of life.对来自生命三界的蛋白质中天然无序结构的预测与功能分析。
J Mol Biol. 2004 Mar 26;337(3):635-45. doi: 10.1016/j.jmb.2004.02.002.
9
Protein disorder prediction: implications for structural proteomics.蛋白质无序预测：对结构蛋白质组学的影响。
Structure. 2003 Nov;11(11):1453-9. doi: 10.1016/j.str.2003.10.002.
10
Intrinsically unstructured proteins evolve by repeat expansion.
Bioessays. 2003 Sep;25(9):847-55. doi: 10.1002/bies.10324.
Zotero 插件