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  • 1
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1983-02-11
    Description: Plasmids were constructed to direct synthesis of the human interferons IFN-alpha 1, IFN-alpha 2, and IFN-gamma in the yeast Saccharomyces cerevisiae. Expression of IFN genes containing coding sequences for secretion signals resulted in the secretion of IFN activity. A large proportion of the IFN-alpha 1 and IFN-alpha 2 isolated from the yeast cell growth media had the same amino termini as the natural mature interferons, suggesting a removal of the signal sequences identical to that of human cells. These results show that a lower eukaryote, such as yeast, can utilize and process a human signal sequence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hitzeman, R A -- Leung, D W -- Perry, L J -- Kohr, W J -- Levine, H L -- Goeddel, D V -- New York, N.Y. -- Science. 1983 Feb 11;219(4585):620-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6186023" target="_blank"〉PubMed〈/a〉
    Keywords: Cloning, Molecular ; Gene Expression Regulation ; Humans ; Interferons/*genetics/secretion ; Peptides/physiology ; Plasmids ; Protein Processing, Post-Translational ; Protein Sorting Signals ; RNA Processing, Post-Transcriptional ; Saccharomyces cerevisiae/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2016-11-09
    Description: Two-component signaling (TCS) is the primary means by which bacteria sense and respond to the environment. TCS involves two partner proteins working in tandem, which interact to perform cellular functions whereas limiting interactions with non-partners (i.e., cross-talk). We construct a Potts model for TCS that can quantitatively predict how mutating amino acid identities affect the interaction between TCS partners and non-partners. The parameters of this model are inferred directly from protein sequence data. This approach drastically reduces the computational complexity of exploring the sequence-space of TCS proteins. As a stringent test, we compare its predictions to a recent comprehensive mutational study, which characterized the functionality of 20 4 mutational variants of the PhoQ kinase in Escherichia coli . We find that our best predictions accurately reproduce the amino acid combinations found in experiment, which enable functional signaling with its partner PhoP. These predictions demonstrate the evolutionary pressure to preserve the interaction between TCS partners as well as prevent unwanted cross-talk. Further, we calculate the mutational change in the binding affinity between PhoQ and PhoP, providing an estimate to the amount of destabilization needed to disrupt TCS.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
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