Ehrlichia chaffeensis TRP120 nucleomodulin binds DNA with disordered tandem repeat domain
| Autor: | Kyung H. Choi, Paige S. Dunphy, Nadia Füllbrunn, Tierra R. Farris, Krishna Rajarathnam, Valerie J. Klema, Jere W. McBride, Krishna Mohan Sepuru |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Protein Folding Magnetic Resonance Spectroscopy Gene Expression Spectrum analysis techniques Biochemistry Database and Informatics Methods chemistry.chemical_compound Gene expression Macromolecular Structure Analysis Ehrlichia chaffeensis Multidisciplinary biology Effector Circular Dichroism Hydrogen-Ion Concentration Antibodies Bacterial Cell biology Chemistry Tandem Repeat Sequences Physical Sciences Host-Pathogen Interactions Medicine Sequence Analysis Research Article Transcriptional Activation Protein Structure Bioinformatics Ultraviolet Rays Sequence analysis Science DNA transcription Active Transport Cell Nucleus Research and Analysis Methods Phosphates 03 medical and health sciences NMR spectroscopy Bacterial Proteins Protein Domains Tandem repeat Sequence Motif Analysis DNA-binding proteins Genetics Humans Gene Regulation Molecular Biology Transcription factor Cell Nucleus Microbial Viability Biology and life sciences Eukaryotic transcription Chemical Compounds Ehrlichiosis Proteins DNA biology.organism_classification Regulatory Proteins Intrinsically Disordered Proteins 030104 developmental biology chemistry Trans-Activators Transcription Factors |
| Zdroj: | PLoS ONE PLoS ONE, Vol 13, Iss 4, p e0194891 (2018) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0194891 |
| Popis: | Ehrlichia chaffeensis, the causative agent of human monocytotropic ehrlichiosis, secretes several effector proteins that bind host DNA to modulate host gene expression. The tandem repeat protein 120 (TRP120), one of the largest effector proteins, has four nearly identical tandem repeat (TR) regions that each consists of 80 amino acids. In addition to playing a role in ehrlichial binding and internalization, TRP120 translocates to the host nucleus where it is thought to function as a transcription factor that modulates gene expression. However, sequence analysis of TRP120 does not identify the presence of DNA-binding or trans-activation domains typical of classical eukaryotic transcription factors. Thus, the mechanism by which TRP120 binds DNA and modulates gene expression remains elusive. Herein, we expressed the TR regions of the TRP120 protein, and characterized its solution structure and ability to bind DNA. TRP120, expressed as either a one or two TR repeat, is a monomer in solution, and is mostly disordered as determined by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. Using NMR spectroscopy, we further show that the 1 TR construct selectively binds GC-rich DNA. Although low pH was required for TRP120 TR-DNA interaction, acidic pH alone does not induce any significant structural changes in the TR region. This suggests that TRP120 folds into an ordered structure upon forming a protein-DNA complex, and thus folding of TRP120 TR is coupled with DNA binding. |
| Databáze: | OpenAIRE |
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