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Title 

Broad spectrum thiopeptide recognition specificity of the Streptomyces lividans tipAL protein and its role in regulating gene expression

Authors 

Mark L ChiuMarc FolchertTakaaki KatohAnna Maria PugliaJiri VohradskyBong Sik YunHaruo SetoCharles J Thompson

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

1999

Citation 

Journal of Biological Chemistry, vol. 274, no. 29, pp. 20578-20586

Keywords 

bacterial proteinprotein tipaldrug protein bindinggene disruptiongene expressiongene expression regulationmolecular recognitionprotein synthesisstreptomyces lividans

Abstract 

Microbial metabolites isolated in screening programs for their ability to activate transcription of the tipA promoter (ptipA) in Streptomyces lividans define a class of cyclic thiopeptide antibiotics having dehydroalanine side chains ('tails'). Here we show that such compounds of heterogeneous primary structure (representatives tested: thiostrepton, nosiheptide, berninamycin, promothiocin) are all recognized by TipAS and TipAL, two in-frame translation products of the tipA gene. The N-terminal helix-turn-helix DNA binding motif of TipAL is homologous to the MerR family of transcriptional activators, while the C terminus forms a novel ligand- binding domain, ptipA inducers formed irreversible complexes in vitro and in vivo (presumably covalent) with TipAS by reacting with the second of the two C-terminal cysteine residues. Promothiocin and thiostrepton derivatives in which the dehydroalanine side chains were removed lost the ability to modify TipAS. They were able to induce expression of ptipA as well as the tipA gene, although with reduced activity. Thus, TipA required the thiopeptide ring structure for recognition, while the tail served either as a dispensable part of the recognition domain and/or locked thiopeptides onto TipA proteins, thus leading to an irreversible transcriptional activation. Construction and analysis of a disruption mutant showed that tipA was autogenously regulated and conferred thiopeptide resistance. Thiostrepton induced the synthesis of other proteins, some of which did not require tipA.

ISSN 

0021-9258

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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