Solution Structure of the Mycobacterium tuberculosis Complex Protein MPB70: From tuberculosis pathogenesis to inherited human corneal disease

Mark D. Carr*, Marieke J. Bloemink, Ellen Dentten, Adam O. Whelan, Stephen V. Gordon, Geoff Kelly, Thomas A. Frenkiel, R. Glyn Hewinson, Richard A. Williamson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Citations (SciVal)

Abstract

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 βig-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 βig-h3) and furthermore that some of the human corneal disease-inducing substitutions identified in βig-h3 will perturb interactions at these sites.

Original languageEnglish
Pages (from-to)43736-43743
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number44
DOIs
Publication statusPublished - 31 Oct 2003

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