Structural Properties and Evolutionary Relationships of PspA, a Surface Protein of Streptococcus pneumoniae, as Revealed by Sequence Analysis

Analysis of the sequence for the gene encoding PspA (pneumococcal surface protein A) of Streptococcus pneumoniae revealed the presence of four distinct domains in the mature protein. The structure of the N-terminal half of PspA was highly consistent with that of an a-helical coiled-coil protein. The a-helical domain was followed by a proline-rich domain (with two regions in which 18 of 43 and 5 of 11 of the residues are prolines) and a repeat domain consisting of 10 highly conserved 20-amino-acid repeats. A fourth domain consisting of a hydrophobic region too short to serve as a membrane anchor and a poorly charged region followed the repeats and preceded the translation stop codon. The C-terminal region of PspA did not possess features conserved among numerous other surface proteins, suggesting that PspA is attached to the cell by a mechanism unique among known surface proteins of gram-positive bacteria. The repeat domain of PspA was found to have significant homology with C-terminal repeat regions of proteins from Streptococcus mutans, Streptococcus downei, Clostridium difficile, and S. pneumoniae. Comparisons of these regions with respect to functions and homologies suggested that, through evolution, the repeat regions may have lost or gained a mechanism for attachment to the bacterial cell. Among gram-positive bacteria, a number of surface pro-teins have been identified and characterized with respect to their structural, virulence, or immunogenic features (19, 22, 25, 31, 62). The amino-terminal regions of these molecules often share the properties of environmental exposure and variability, although their structural similarities may be limited. In contrast, the carboxy termini of many of these proteins show extensive similarities in their cell-associated regions, suggesting that a common mechanism for attachin