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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