Background:Staphylococcus aureus has evolved a web of mechanisms to disrupt the human complement system. Results: We report the structures of two staphylococcal complement inhibitor proteins, SCIN-B and SCIN-D. Conclusion:We have identified differences in C3b recognition within active SCIN proteins and suggest a physical basis for lack of C3b binding by SCIN-D. Significance: This analysis may inform future design of complement-targeted therapeutics.

Authors are urged to introduce these corrections into any reprints they distribute. Secondary (abstract) services are urged to carry notice of these corrections as prominently as they carried the original abstracts.

MR.A preferential p110␣/␥ PI3K inhibitor attenuates experimental inflammation by suppressing the production of proinflammatory mediators in a NF-Bdependent manner.

No abstract

bRibosomal proteins S4 and S5 participate in the decoding and assembly processes on the ribosome and the interaction with specific antibiotic inhibitors of translation. Many of the characterized mutations affecting these proteins decrease the accuracy of translation, leading to a ribosomal-ambiguity phenotype. Structural analyses of ribosomal complexes indicate that the tRNA selection pathway involves a transition between the closed and open conformations of the 30S ribosomal subunit and requires disruption of the interface between the S4 and S5 proteins. In agreement with this observation, several of the mutations that promote miscoding alter residues located at the S4-S5 interface. Here, the Escherichia coli rpsD and rpsE genes encoding the S4 and S5 proteins were targeted for mutagenesis and screened for accuracy-altering mutations. While a majority of the 38 mutant proteins recovered decrease the accuracy of translation, error-restrictive mutations were also recovered; only a minority of the mutant proteins affected rRNA processing, ribosome assembly, or interactions with antibiotics. Several of the mutations affect residues at the S4-S5 interface. These include five nonsense mutations that generate C-terminal truncations of S4. These truncations are predicted to destabilize the S4-S5 interface and, consistent with the domain closure model, all have ribosomal-ambiguity phenotypes. A substantial number of the mutations alter distant locations and conceivably affect tRNA selection through indirect effects on the S4-S5 interface or by altering interactions with adjacent ribosomal proteins and 16S rRNA. C ellular protein synthesis systems translate mRNAs quickly and with high accuracy. The accuracy of the decoding process can, however, be altered by agents such as the antibiotic streptomycin that promote miscoding and by mutations in rRNA, ribosomal proteins, or translation factors (1). Among the first such accuracy mutants to be characterized were some of the streptomycin-resistant Escherichia coli strains carrying alterations in ribosomal protein S12 (2). Subsequently, E. coli mutants carrying altered ribosomal protein S4 or S5 were isolated that supported increased levels of miscoding (3-5). Since those early studies, many other mutants have been isolated that affect the accuracy of decoding and carry alterations in different components of the translation machinery (1, 4).The determination of high-resolution structures of ribosomes has offered structural interpretations of the effects of some accuracy-altering ribosomal mutations (6). X-ray crystallography of ribosomal complexes has shown that conserved RNA elements of the decoding center use a shape-sensing mechanism to monitor base pairing between the A site codon and the anticodon of incoming aminoacyl-tRNA. Successful interaction of a ternary complex of EF-Tu-GTP-aminoacyl-tRNA with mRNA in the decoding center triggers a series of conformational rearrangements of the head and shoulder domains of the 30S subunit, ultimately resulting in the formation of a ...