Solution structure of the Mycobacterium tuberculosis complex protein MPB70: from tuberculosis pathogenesis to inherited human corneal desease.
The closely related mycobacteria responsible for tuberculosis produce an unusually high number of secreted proteins, many of which are clearly implicated in pathogenesis and protective immunity. Falling within this category are the closely related proteins MPB70 and MPB83. The structure of MPB70 reveals a complex and novel bacterial fold, which has clear structural homology to the two C-terminal FAS1 domains of the cell adhesion protein fasciclin I, whose structures were reported very recently. Assessment of the surface features of MPB70, the sequence divergence between MPB70 and MPB83, the conservation of residues across a group of FAS1 domains, and the locations of disease-inducing mutations in betaig-h3 strongly suggests that MPB70 and MPB83 contain two functional surfaces on opposite faces, which are probably involved in binding to host cell proteins. This analysis also suggests that these functional surfaces are retained in the FAS1 proteins associated with mediating interactions between cells and the extracellular matrix (fasciclin I, periostin, and betaig-h3) and furthermore that some of the human corneal disease-inducing substitutions identified in betaig-h3 will perturb interactions at these sites.
Carr
Mark D
MD
Department of Biochemistry, University of Leicester, Adrian Bldg., University Road, Leicester LE1 7RH United Kingdom. mdc12@le.ac.uk
Bloemink
Marieke J
MJ
Dentten
Ellen
E
Whelan
Adam O
AO
Gordon
Stephen V
SV
Kelly
Geoff
G
Frenkiel
Thomas A
TA
Hewinson
R Glyn
RG
Williamson
Richard A
RA
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry; D003316:Corneal Diseases / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D016212:Transforming Growth Factor beta; D014376:Tuberculosis / Q000382:microbiology*; D000099222:betaIG-H3 Protein
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C094904:MPB83 protein, Mycobacterium; C512835:POSTN protein, human; C051641:fasciclin I; C060216:MPB70 protein, Mycobacterium bovis