Novel fold and assembly of the repetitive B region of the Staphylococcus aureus collagen-binding surface protein

Background: The Staphylococcus aureus collagen-binding protein Cna mediates bacterial adherence to collagen, The primary sequence of Cna has a non-rep etitive collagen-binding A region, followed by the repetitive B region. The B region has one to four 23 kDa repeat units (B-1-B-4), depending on the s train of origin. The affinity of the A region for collagen is independent o f the B region, However, the B repeat units have been suggested to serve as a 'stalk' that projects the A region from the bacterial surface and thus f acilitate bacterial adherence to collagen. To understand the biological rol e of these B-region repeats we determined their three-dimensional structure . Results: B-1 has two domains (D-1 and D-2) placed side-by-side. D-1 and D-2 have similar secondary structure and exhibit a unique fold that resembles but is the inverse of the immunoglobulin-like (IgG-like) domains. Compariso n with similar immunoglobulin superfamily (IgSF) structures shows novel pac king arrangements between the D-1 and D-2 domains. In the B1B2 crystal stru cture, an omission of a single glycine residue in the D-2-D-3 linker loop, compared to the D-1-D-2 and D-3-D-4 linker loops, resulted in projection of the D-3 and D-4 in a spatially new orientation. We also present a model fo r B1B2B3B4. Conclusions: The B region of the Cna collagen adhesin has a novel fold that is reminiscent of but is inverse in nature to the IgG fold. This B region assembly could effectively provide the needed flexibility and stability for presenting the ligand binding A region away from the bacterial cell surfac e.