结核杆菌毒力因子CFP-10和ESAT-6所形成复合物的结构与功能
Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6.
作者信息
Renshaw Philip S, Lightbody Kirsty L, Veverka Vaclav, Muskett Fred W, Kelly Geoff, Frenkiel Thomas A, Gordon Stephen V, Hewinson R Glyn, Burke Bernard, Norman Jim, Williamson Richard A, Carr Mark D
机构信息
Department of Biochemistry, University of Leicester, Leicester, UK.
出版信息
EMBO J. 2005 Jul 20;24(14):2491-8. doi: 10.1038/sj.emboj.7600732. Epub 2005 Jun 23.
Abstract
The secreted Mycobacterium tuberculosis complex proteins CFP-10 and ESAT-6 have recently been shown to play an essential role in tuberculosis pathogenesis. We have determined the solution structure of the tight, 1:1 complex formed by CFP-10 and ESAT-6, and employed fluorescence microscopy to demonstrate specific binding of the complex to the surface of macrophage and monocyte cells. A striking feature of the complex is the long flexible arm formed by the C-terminus of CFP-10, which was found to be essential for binding to the surface of cells. The surface features of the CFP-10.ESAT-6 complex, together with observed binding to specific host cells, strongly suggest a key signalling role for the complex, in which binding to cell surface receptors leads to modulation of host cell behaviour to the advantage of the pathogen.
摘要
最近研究表明，分泌型结核分枝杆菌复合蛋白CFP-10和ESAT-6在结核病发病机制中起着至关重要的作用。我们已经确定了CFP-10和ESAT-6形成的紧密1:1复合物的溶液结构，并利用荧光显微镜证明该复合物与巨噬细胞和单核细胞表面的特异性结合。该复合物的一个显著特征是由CFP-10的C末端形成的长柔性臂，发现它对于与细胞表面结合至关重要。CFP-10.ESAT-6复合物的表面特征，以及观察到的与特定宿主细胞的结合，强烈表明该复合物具有关键的信号传导作用，其中与细胞表面受体的结合导致宿主细胞行为的调节，从而有利于病原体。
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本文引用的文献
1
The program XEASY for computer-supported NMR spectral analysis of biological macromolecules.
J Biomol NMR. 1995 Jul;6(1):1-10. doi: 10.1007/BF00417486.
2
Sequence-specific assignment and secondary structure determination of the 195-residue complex formed by the Mycobacterium tuberculosis proteins CFP-10 and ESAT-6.
J Biomol NMR. 2004 Oct;30(2):225-6. doi: 10.1023/B:JNMR.0000048852.40853.5c.
3
Tuberculous granuloma formation is enhanced by a mycobacterium virulence determinant.
PLoS Biol. 2004 Nov;2(11):e367. doi: 10.1371/journal.pbio.0020367. Epub 2004 Oct 26.
4
Characterisation of complex formation between members of the Mycobacterium tuberculosis complex CFP-10/ESAT-6 protein family: towards an understanding of the rules governing complex formation and thereby functional flexibility.
FEMS Microbiol Lett. 2004 Sep 1;238(1):255-62. doi: 10.1016/j.femsle.2004.07.043.
5
Individual RD1-region genes are required for export of ESAT-6/CFP-10 and for virulence of Mycobacterium tuberculosis.
Mol Microbiol. 2004 Jan;51(2):359-70. doi: 10.1046/j.1365-2958.2003.03844.x.
6
Genetic requirements for mycobacterial survival during infection.
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12989-94. doi: 10.1073/pnas.2134250100. Epub 2003 Oct 20.
7
The primary mechanism of attenuation of bacillus Calmette-Guerin is a loss of secreted lytic function required for invasion of lung interstitial tissue.
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12420-5. doi: 10.1073/pnas.1635213100. Epub 2003 Oct 13.
8
Acute infection and macrophage subversion by Mycobacterium tuberculosis require a specialized secretion system.
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13001-6. doi: 10.1073/pnas.2235593100. Epub 2003 Oct 13.
9
Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment.
J Exp Med. 2003 Sep 1;198(5):693-704. doi: 10.1084/jem.20030846.
10
Solution structure of the Mycobacterium tuberculosis complex protein MPB70: from tuberculosis pathogenesis to inherited human corneal desease.
J Biol Chem. 2003 Oct 31;278(44):43736-43. doi: 10.1074/jbc.M307235200. Epub 2003 Aug 12.
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