A1 Refereed original research article in a scientific journal
A nested gene in Streptomyces bacteria encodes a protein involved in quaternary complex formation
Authors: Kallio P, Liu ZL, Mantsala P, Niemi J, Metsa-Ketela M
Publisher: ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
Publication year: 2008
Journal name in source: JOURNAL OF MOLECULAR BIOLOGY
Journal acronym: J MOL BIOL
Volume: 375
Issue: 5
First page : 1212
Last page: 1221
Number of pages: 10
ISSN: 0022-2836
DOI: https://doi.org/10.1016/j.jmb.2007.11.044
Abstract
The gene pgaM is involved in the biosynthesis of an angucycline-type polyketide antibiotic in Streptomyces sp. PGA64. It encodes a two-domain polypeptide consisting of an N-terminal flavoprotein oxygenase and a C-terminal short-chain alcohol. dehydrogenase/reductase, which are fused together at the translational level as a result of end codon deletion. Here we show that translation also initiates at an internal start codon that enables independent expression of a separate reductase subunit, PgaMred. This confirms that the gene exhibits a rare viral-like arrangement of two overlapping reading frames that allows simultaneous expression of two alternative forms of the protein. Together, these two proteins associate to form a stable non-covalent complex, the native form of PgaM. The reductase subunit PgaMred is shown to provide enzyme stability and to affect the redox state of the oxygenase domain FAD. Finally, a model for the quaternary structure of the complex that explains the necessity for a nested gene system and the unusual behaviour of the protein subunits in vitro is presented. (C) 2007 Elsevier Ltd. All rights reserved.
The gene pgaM is involved in the biosynthesis of an angucycline-type polyketide antibiotic in Streptomyces sp. PGA64. It encodes a two-domain polypeptide consisting of an N-terminal flavoprotein oxygenase and a C-terminal short-chain alcohol. dehydrogenase/reductase, which are fused together at the translational level as a result of end codon deletion. Here we show that translation also initiates at an internal start codon that enables independent expression of a separate reductase subunit, PgaMred. This confirms that the gene exhibits a rare viral-like arrangement of two overlapping reading frames that allows simultaneous expression of two alternative forms of the protein. Together, these two proteins associate to form a stable non-covalent complex, the native form of PgaM. The reductase subunit PgaMred is shown to provide enzyme stability and to affect the redox state of the oxygenase domain FAD. Finally, a model for the quaternary structure of the complex that explains the necessity for a nested gene system and the unusual behaviour of the protein subunits in vitro is presented. (C) 2007 Elsevier Ltd. All rights reserved.
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