Molecular basis of the recognition of the ap65-1 gene transcription promoter elements by a Myb protein from the protozoan parasite Trichomonas vaginalis
| Autor: | Tai Huang Huang, Wen-Jin Wu, Yen Chywan Liaw, Sheng Chia Chen, Jung-Hsiang Tai, Szu Huan Wang, Imamaddin Amiraslanov, Chen Kun Tsai, Ingjye Jiang, Chi Fon Chang |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Genetics Molecular Sequence Data Response element Protozoan Proteins Promoter DNA Biology Crystallography X-Ray Cell biology Structural Biology Trichomonas vaginalis Thermodynamics Proto-Oncogene Proteins c-myb MYB Amino Acid Sequence Binding site Promoter Regions Genetic Cell Adhesion Molecules Nuclear Magnetic Resonance Biomolecular Gene Transcription factor Peptide sequence Protein Binding |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkr558 |
| Popis: | Iron-inducible transcription of the ap65-1 gene in Trichomonas vaginalis involves at least three Myb-like transcriptional factors (tvMyb1, tvMyb2 and tvMyb3) that differentially bind to two closely spaced promoter sites, MRE-1/MRE-2r and MRE-2f. Here, we defined a fragment of tvMyb2 comprising residues 40-156 (tvMyb2₄₀₋₁₅₆) as the minimum structural unit that retains near full binding affinity with the promoter DNAs. Like c-Myb in vertebrates, the DNA-free tvMyb2₄₀₋₁₅₆ has a flexible and open conformation. Upon binding to the promoter DNA elements, tvMyb2₄₀₋₁₅₆ undergoes significant conformational re-arrangement and structure stabilization. Crystal structures of tvMyb2₄₀₋₁₅₆ in complex with promoter element-containing DNA oligomers showed that 5'-a/gACGAT-3' is the specific base sequence recognized by tvMyb2₄₀₋₁₅₆, which does not fully conform to that of the Myb binding site sequence. Furthermore, Lys⁴⁹, which is upstream of the R2 motif (amino acids 52-102) also participates in specific DNA sequence recognition. Intriguingly, tvMyb2₄₀₋₁₅₆ binds to the promoter elements in an orientation opposite to that proposed in the HADDOCK model of the tvMyb1₃₅₋₁₄₁/MRE-1-MRE-2r complex. These results shed new light on understanding the molecular mechanism of Myb-DNA recognition and provide a framework to study the molecular basis of transcriptional regulation of myriad Mybs in T. vaginalis. |
| Databáze: | OpenAIRE |
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