CRYSTAL STRUCTURE OF ACE19: A COLLEGEN BINDING MSCRAMM FROM Enterococcus faecalis

CRYSTAL STRUCTURE OF ACE19: A COLLEGEN BINDING MSCRAMM FROM Enterococcus faecalis

Karthe Ponnuraj,^a Yi Xu,^b Damon Choe,^bDwight Moore,^a Magnus Hook^b and Sthanam V. L. Narayana^a

^aCenter for Biophysical Sciences and Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA; ^bInstitute of Biosciences and Technology, Texas Medical Center, Houston, TX 77030, USA (karthe@bharathi.cbse.uab.edu)

Many potentially pathogenic bacteria bind to extracellular matrix (ECM) proteins such as fibrinogen, fibronectin, laminin and collagen. MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) represent a subfamily of bacterial adhesins that specifically bind to ECM molecules. Adherence of bacterial pathogens to ECM proteins of the host initiates colonization and this is the critical first event in a multistep process that may lead to infection.

Enterococcus faecalis is an opportunistic pathogen known to cause many infections such as septicemia and urinary tract infections in humans. Ace is a collagen-binding cell surface adhesin from E. faecalis [1]. Ace19 is the truncated form of Ace40, the full-length collagen-binding domain of Ace. Ace19 exhibits a high sequence similarity with Cna19, the minimum collagen-binding domain of Cna from S. aureus. Modeling studies suggested that Ace19 have Cna19-like structure with a collagen-binding trench-shaped motif traversing the surface. However, kinetic studies indicate that the mechanism of collagen binding is significantly distinct for these proteins [1]. This suggests two homologous MSCRAMM proteins interact with a common ligand, the collagen, with two different modes. In order to identify critical residues and also the nature of the collagen-binding site in Ace19 we have crystallized [2] and solved the structure of Ace19 by Multiple Isomorphous Replacement method. Although the structure of Ace19 is very identical to Cna19, significant differences are observed at few places on the surface of the ligand binding trench.

References

1 Rich, R. L., Kreikemeyer, B., Owens, R. T., LaBrenz, S., Narayana, S. V. L., Weinstock, G. M., Murray, B. E. and Hook, M. (1999), J. Biol. Chem. 274, 26939-26945.

2 Ponnuraj, K., Xu, Y., Moore, D., Deivanayagam, C. C. S., Boque, L., Hook, M. and Narayana, S. V. L. (2002), Biochimica et Biophysica Acta. 1596, 173-176.