STRUCTURAL AND FUNCTIONAL ANALOGY BETWEEN PNEUMOLYSIN AND PROAEROLYSIN

Pneumolysin and proaerolysin are bacterial toxins that form pores in h ost cells by oligomerization. We propose that they may have similar st ructures despite a poor sequence identity. The crystal structure of pr oaerolysin reveals a protein composed of four domains, arranged in the shape of an elongated comma. Electron microscopy of the pneumolysin m onomer shows a similar arrangement of domains. The sequence of pneumol ysin recognizes the template of proaerolysin from a library of protein folds. A three-dimensional model of pneumolysin has been constructed by the comparative approach using the structure of proaerolysin. This model, together with results on the activity of site-specific mutants and the positions of antigenic sites, has been used to propose functio nal roles of individual domains.