Biomedical subjects

S G Andersson

Publications and source records attributed to S G Andersson.

5 recordsLinked to original sources

PubMed1990

Codon preferences in free-living microorganisms.

A popular interpretation of the major codon preference is that it reflects the operation of a regulatory device that controls the expression of individual proteins. In this popular model, rapidly translated codons are thought to promote the accumulation of the highly expressed proteins and slowly translated codons are thought to retard the expression of poorly expressed proteins. However, this widely accepted model is not supported by kinetic theory or by experimental results. A less fashionable model in which the major codon preference has nothing to do with the expression level of the individual proteins is forwarded. In this model, the major codon preference is viewed as a global strategy to support the efficient function of the translation system and thereby to maximize the growth rates of cells under favorable conditions.

Animals↗

PubMed1988

Effects of erythromycin base and erythromycin esters on protein synthesis in vivo in Escherichia coli.

The inhibitory effects on protein synthesis in vivo of erythromycin base and several erythromycin esters have been determined. An experimental method was used, especially suited for studies on short-lived antibiotics causing low levels of inhibition. Most of the tested derivatives were 2-3% as active as erythromycin base while a split product of erythromycin, anhydroerythromycin, was 4% as effective.

Bacterial Proteins↗

PubMed1986

Functional interactions between mutated forms of ribosomal proteins S4, S5 and S12.

Here we show that ram mutations, either in ribosomal protein S4 or S5, decrease the proofreading flows for both cognate and noncognate ternary complexes bound by streptomycin-dependent (SmD) ribosomes. This effect is accompanied by a slight increase in the overall error frequency. More important, however, is the decreased proofreading of the cognate species which is almost reduced to wild-type levels. The data suggest that it may be the reduction of the proofreading of the cognate substrate that is important for suppressing streptomycin dependence. Furthermore, we show that rpsE mutants, selected from streptomycin-dependent strains, behave kinetically very similarly to the previously described rpsD mutants.

Codon↗

PubMed1984

Does codon composition influence ribosome function?

Escherichia coli ribosomes pre-initiated with N-acetyl-Val-tRNAVal elongate strictly alternating poly(U-G) at a rate between eight and 12 peptide bonds per second per ribosome in vitro. Comparisons with poly(U)-primed poly(Phe) synthesis show that these systems function with the same rates which are close to those of protein synthesis in vivo. This indicates that, at least in vitro, codon composition has no marked influence on the speed of elongation when the concentration of ternary complex is saturating. Furthermore, the missense frequencies for the two polymers are within the same range: the missense substitution of Trp for Cys is 10(-4) and that of Met for Val is 10(-3) in the poly(U-G)-primed system. These data argue against models that explain the codon preference of certain gene families by postulating effects of high or low GC content of codons on the performance characteristics of ribosomes.

Codon↗

PubMed1984

ppGpp inhibition of elongation factors Tu, G and Ts during polypeptide synthesis.

The inhibition of elongation factors G, Tu and Ts by ppGpp was studied in vitro in a translation system with missense frequency and elongation rate similar to those in vivo. ppGpp inhibits EF-G with KI = 6 X 10(-5) M. When ppGpp is in twofold excess over GTP and EF-G is the rate-limiting component, the elongation rate is reduced twofold by ppGpp. EF-Tu is inhibited with KI = 7 X 10(-7) M in the absence of EF-Ts. When EF-Ts is added, the binding of ppGpp to EF-Tu becomes successively weaker. 1/KI depends linearly on 1/[Ts] and the intercept at the abscissa gives KI = 4 X 10(-5) M. This reflects the binding of ppGpp to the binary TuTs complex. The slope reveals that the binding of EF-Ts to the TuMS binary complex is strong (10(-6) M). ppGpp may thus inhibit the cycling of EF-Tu indirectly by the removal of the free EF-Ts by its adsorption to TuMS, as well as directly by simple binding to Tu. EF-Tu inhibition by ppGpp can be fully reversed by high levels of aminoacyl-tRNA only in the presence of EF-Ts and at low ribosomal activity. Our in vitro observations have been extrapolated to in vivo conditions with conclusions as follows: Under strong amino acid starvation ppGpp in twofold excess over GTP cannot reduce significantly the elongation rate of ribosomes and thereby restore the errors to their normal levels as in the stringent response. Under weak starvation, in contrast, a significant rate reduction can be achieved by the trapping of EF-Ts in complex with TuppGpp.

Bacterial Proteins↗