Biomedical subjects

C S Cameron

Publications and source records attributed to C S Cameron.

9 recordsLinked to original sources

PubMed1997

The stability and dynamics of ribosomal protein L9: investigations of a molecular strut by amide proton exchange and circular dichroism.

Nuclear magnetic resonance and circular dichroism experiments were used to investigate the stability and dynamic aspects of ribosomal protein L9 from Bacillus stearothermophilus in solution. This unusually shaped protein, with its two widely spaced RNA-binding domains linked by a connecting helix, has been hypothesized to serve as a "molecular strut", most likely playing a role in ribosome assembly and/or maintaining the catalytically active conformation of ribosomal RNA. Protection factors for amide proton exchange were quantitatively measured in an extensive series of NMR experiments, providing probes of the stability and dynamics of localized regions of the protein. Results show that each of the two RNA-binding domains contains a highly stable core. The exposed central helix that connects the two domains is helical in solution, albeit not rigid, a result that is supported by amide proton protection factors, circular dichroism measurements, and carbon-13 and proton chemical shift index values. A conserved glycine and lysine-rich loop in the N-terminal domain is ordered and quite stable, a surprising result, since this loop had been presumed to be disordered in the original crystallographic analysis. Interestingly, the most dynamic parts of the protein are the regions that contain the likely RNA-binding residues in each of the two domains. The present results add further support to the notion that the L9 protein plays an architectural role within the ribosome, with the central helix serving as a molecular strut, or perhaps a spring, linking the two widely spaced RNA-binding domains.

Amides↗

PubMed1996

Ribosomal protein L9: a structure determination by the combined use of X-ray crystallography and NMR spectroscopy.

The structure of protein L9 from the Bacillus stearothernophilus ribosome has been determined at 2.5 A resolution by refinement against single crystal X-ray diffraction data with additional constraints provided by NMR data. This highly elongated protein consists of two domains separated by a nine-turn connecting helix. Conserved aromatic and positively charged amino acid residues on the surface of each domain are likely to be directly involved in binding 23 S ribosomal RNA. The shape of the protein, with its two widely spaced RNA-binding sites, suggests that it may serve as a "molecular strut", most likely playing a role in ribosome assembly and/or maintaining the catalytically active conformation of the ribosomal RNA. The combined use of X-ray and NMR data in the refinement procedure was essential in defining the N-terminal domain of the protein, which was relatively poorly determined by the X-ray data alone. In addition to resolving the ambiguities in defining the hydrophobic core and side-chain conformations with the N-terminal domain, this combined NMR-X-ray analysis provides the first detailed and accurate view of the N-terminal RNA-binding site. NMR data also showed that the N-terminal domain is stable in solution, indicated by amide protons that are protected from solvent exchange. The lack of definition of the N-terminal domain in the X-ray structure is therefore likely due to packing disorder within the crystal rather than structural instability. This combined NMR-X-ray analysis provides a useful model as to how X-ray and NMR data can be practically and logically combined in the determination of the structure of a single protein molecule.

Amino Acid Sequence↗

PubMed1989

Cost-effectiveness of routine and campaign vaccination strategies in Ecuador.

A national household coverage survey of 3697 Ecuadorean children, carried out in July 1986, provided an opportunity for a cost-effectiveness analysis of (1) routine vaccination services based in fixed facilities and (2) mass immunization campaigns. A major purpose of the campaigns was to complement the routine services and to accelerate immunization activities. Based on the coverage survey, the Program for Reduction of Maternal and Childhood Illness (PREMI) and earlier campaigns increased the proportion of children under 5 years who were fully vaccinated from 43% to 64%. In one year, the PREMI campaign was responsible for fully vaccinating 11% of children under one year, 21% of 1-2-year-old children, and 13% of all children under 5 years. The campaign also helped ensure that vaccinations were completed when children were still very young and at greatest risk. The average cost per vaccination dose (in 1985 US$ prices) was approximately $0.29 for fixed facilities and $0.83 for the PREMI campaign. Total national costs were $675,000 and $1,665,000 for routine and campaign services respectively. The cost per fully vaccinated child (FVC) was $4.39 for routine vaccination services and $8.60 for the campaign. The cost per death averted was about $1900 for routine vaccination services, $4200 for the PREMI campaign, and $3200 for the combined programme. Because of Ecuador's lower mortality rates, the costs per death averted in Ecuador from both vaccination strategies are not as low as those from studies of vaccinations in Africa. The campaigns, though less cost-effective than routine services, significantly improved the vaccination coverage of younger children who had been missed by the routine services. The costs per FVC of both the campaign and the routine services compare favourably with such programmes in other countries.

Child↗

PubMed1974