Homology between proteins controlling Streptomyces fradiae tylosin resistance and ATP-binding transport

• Published in: Gene Vol. 102; no. 1; pp. 27 - 32
• Main Authors: Rosteck, Paul R., Reynolds, Patricia A., Hershberger, Charles L.
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 15.06.1991; Amsterdam Elsevier; New York, NY
• Subjects: Adenosine Triphosphate - metabolism; Amino Acid Sequence; antibiotic export; antibiotic resistance; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Base Sequence; Binding Sites - genetics; Biological and medical sciences; Carrier Proteins - genetics; Carrier Proteins - metabolism; Drug Resistance, Microbial - genetics; Escherichia coli - genetics; Fundamental and applied biological sciences. Psychology; gene duplication; Gene Expression - physiology; genes; Genes. Genome; Humans; macrolide resistance; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; nucleotide sequence; predictions; products; Recombinant DNA; Sequence Alignment; Sequence Homology, Nucleic Acid; Streptomyces - drug effects; Streptomyces - genetics; Streptomyces - metabolism; Streptomyces fradiae; tlrC; tlrC gene; tylosin; Tylosin - metabolism; Tylosin - pharmacology; aa; ORF; SDS; Ty; nt; rRNA; PAGE; Recombinant DNA; bp; macrolide resistance; nucleotide sequence; tsp; R; antibiotic export; gene duplication; kb; tlr; tlrC; UWGCG; Membrane protein; Streptomycetaceae; Streptomyces fradiae; Nucleotide sequence; Transcription; Gene product; Homology; Actinomycetales; Resistance; Antibiotic; Membrane transport; Bacteria; Actinomycetes; Tylosin; Molecular cloning
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/0378-1119(91)90533-H

A tylosin(Ty)-producing strain of Streptomyces fradiae contains at least three genes, tlrA, tlrB, tlrC, specifying resistance to Ty (Ty R). The complete nucleotide sequence of the Ty R-encoding gene, tlrC, and the transcription start point of the gene were determined. The sequence contains an open reading frame coding for a protein of 548 amino acids (aa) with an M r of 59129. The TlrC protein was identified by expression of the cloned gene by in vitro coupled transcription and translation in cell-free extracts derived from Streptomyces lividans. The N- and C-terminal halves of TlrC share extensive homology, suggesting that the protein evolved through tandem gene duplication. Each half of the deduced TlrC aa sequence also shows significant homology to numerous eukaryotic and prokaryotic membrane-associated, active-transport protein subunits. The homologous proteins include examples from the systems responsible for efflux of cytotoxic drugs from multidrug-resistant human cells and for export of hemolysin from Escherichia coli. The greatest similarity to TlrC is in regions containing the ATP-binding sites found in these proteins. These results suggest a role for the tlrC gene product as part of a multiple component, ATP-dependent transport system for the active excretion of Ty from the producing organism.