Novel fold and assembly of the repetitive B region of the Staphylococcus aureus collagen-binding surface protein.
BACKGROUND
[corrected] The Staphylococcus aureus collagen-binding protein Cna mediates bacterial adherence to collagen. The primary sequence of Cna has a non-repetitive 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 strain of origin. The affinity of the A region for collagen is independent of 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 facilitate bacterial adherence to collagen. To understand the biological role 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. Comparison with similar immunoglobulin superfamily (IgSF) structures shows novel packing arrangements between the D(1) and D(2) domains. In the B(1)B(2) crystal structure, 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 for B(1)B(2)B(3)B(4).


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 surface.
Deivanayagam
C C
CC
Center for Macromolecular Crystallography, School of Optometry, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
Rich
R L
RL
Carson
M
M
Owens
R T
RT
Danthuluri
S
S
Bice
T
T
Höök
M
M
Narayana
S V
SV
D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D018360:Crystallography, X-Ray; D007074:Immunoglobulin G / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*; D055672:Static Electricity
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; C048165:adhesin, Staphylococcus aureus; D003094:Collagen