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Activation and Novel Processing of Matrix Metalloproteinases by a Thiol-proteinase from the Oral Anaerobe Porphyromonas gingivalis

'Department of Periodontics, Department of Oral Biology, Rm. 736, BBRB, 845 19th St. S., University of Alabama at Birmingham, Birmingham, Alabama 35294

L.J. Windsor

Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham

M.K. Bodden

Department of Restorative Dentistry, University of Alabama at Birmingham

G.J. Harber

Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham

B. Birkedal-Hansen

Division of Cancer Biology, Diagnosis and Centers, National Cancer Institute

H. Birkedal-Hansen

National Institute of Dental Research, National Institutes of Health

A critical outcome of periodontal disease is degradation of the collagenous periodontal ligament that connects teeth to bone in the dental arch. Periodontal diseases occur in response to bacterial colonization of the teeth, but their molecular pathogenesis is still speculative. One family of enzymes, known as the matrix metalloproteinases (MMPs), has been implicated in the degradation of the periodontal ligament. MMPs, which are also suspected to play a role in many other physiologic and pathologic remodeling processes, can be secreted by epithelial cells surrounding the teeth and are found in relative abundance in tissues and fluids near periodontally diseased sites. Since most MMPs are secreted as inactive zymogens which may be activated by limited proteolysis, it has been suggested that proteinases expressed by the infecting periodontal pathogens might activate latent host MMPs to initiate or accelerate degradation of the collagenous periodontal ligament. The aim of this work was to examine interactions between purified host MMPs and bacterial proteinase. In this article, we demonstrate that a proteinase isolated from the periodontopathogen Porphyromonas gingivalis can activate MMP-1, MMP-3, and MMP-9 and can catalyze the superactivation of MMP-1 by MMP-3. Activation of these MMPs is demonstrated to result from initital hydrolysis within their propeptide. Also, for MMP-1 and MMP-9, the P. gingivalis proteinase cleaves the MMP propeptide following a lysine residue at a previously unreported site which, for both MMPs, is one residue NH2-terminal to the known autocatalytic cleavage site. These data describe a mode of virulence for the periodontopathogen Porphyromonas gingivalis that involves activation of host-degradative enzymes.

Key Words: Metalloproteinases • Porphyromonas gingivalis • cysteine proteinases • amino acid sequencing • Western blotting

Journal of Dental Research, Vol. 76, No. 6, 1260-1270 (1997)
DOI: 10.1177/00220345970760060501


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