Hic, a novel surface protein of Streptococcus pneumoniae that interferes with complement function.
The important human pathogen Streptococcus pneumoniae was found to absorb factor H, an inhibitor of complement, from human plasma. We identified the gene encoding a novel surface protein, factor H-binding inhibitor of complement (Hic), in the pspC locus of type 3 pneumococci. Unlike PspC proteins in other serotypes, Hic is anchored to the cell wall by means of an LPXTG motif, and the overall sequence homology to various PspC proteins is low. However, the NH(2)-terminal region showed significant homology to the NH(2)-terminal region of several PspC proteins. A fragment of Hic, covering this homologous region, was expressed as a glutathione S-transferase (GST) fusion protein. GST:Hic(39-261) bound radiolabeled factor H and inhibited binding of factor H to pneumococci of different serotypes. Interaction kinetics between GST:Hic(39-261) and factor H were studied with surface plasmon resonance and showed a high affinity binding (K(A) = 5 x 10(7), K(D) = 2.3 x 10(-)(8)). Mutant pneumococci lacking Hic showed no absorption of factor H in human plasma and no binding of radiolabeled factor H, suggesting that Hic is responsible for factor H-binding in type 3 pneumococci. Factor H-dependent inhibition of the alternative pathway was not diminished by the presence of GST:Hic(39-261). In addition, an intrinsic inhibitory effect of Hic is suggested.
Janulczyk
R
R
Departments of Cell and Molecular Biology, Section for Molecular Pathogenesis, Laboratory Medicine, Section of MIG, Lund University, 22100 Lund, Sweden. Robert.Janulczyk@medkem.lu.se
Iannelli
F
F
Sjoholm
A G
AG
Pozzi
G
G
Bjorck
L
L
D000483:Alleles; D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D011485:Protein Binding; D013296:Streptococcus pneumoniae / Q000737:chemistry*; D020349:Surface Plasmon Resonance; D013499:Surface Properties
D001426:Bacterial Proteins; C493495:CFH protein, human; D002352:Carrier Proteins; C417512:Hic protein, Streptococcus pneumoniae; D017242:Complement Factor H