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.
Department of Biochemistry, University of Leicester, Leicester, UK.
Philip S
PS
Renshaw
Kirsty L
KL
Lightbody
Vaclav
V
Veverka
Fred W
FW
Muskett
Geoff
G
Kelly
Thomas A
TA
Frenkiel
Stephen V
SV
Gordon
R Glyn
RG
Hewinson
Bernard
B
Burke
Jim
J
Norman
Richard A
RA
Williamson
Mark D
MD
Carr
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