Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6.
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.
Renshaw
Philip S
PS
Department of Biochemistry, University of Leicester, Leicester, UK.
Lightbody
Kirsty L
KL
Veverka
Vaclav
V
Muskett
Fred W
FW
Kelly
Geoff
G
Frenkiel
Thomas A
TA
Gordon
Stephen V
SV
Hewinson
R Glyn
RG
Burke
Bernard
B
Norman
Jim
J
Williamson
Richard A
RA
Carr
Mark D
MD
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D019556:COS Cells; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D041681:NIH 3T3 Cells; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D020298:U937 Cells; D037521:Virulence Factors / Q000737:chemistry* / Q000502:physiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D037521:Virulence Factors