Source:http://linkedlifedata.com/resource/pubmed/id/17497933
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
22
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| pubmed:dateCreated |
2007-5-29
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| pubmed:abstractText |
The polypyrimidine tract binding protein (PTB) is involved in many physiological processes, including alternative splicing, internal ribosomal entry side (IRES)-mediated initiation of translation, and polyadenylation, as well as in ensuring mRNA stability. However, the role of PTB in these processes is not fully understood, and this has motivated us to undertake a computational study of the protein. PTB RNA binding domains (RBDs) 3 and 4 and their complexes with oligopyrimidine RNAs were simulated using the GROMOS simulation software using the GROMOS 45A4 force field. First, the stability and fluctuations of the tertiary fold and of the secondary structural elements in individual domains, the combined RBD34 domain, and their complexes with RNA were studied. Second, the simulation results were validated against the experimental NMR NOE data. The analysis of hydrogen bonding patterns, salt bridge networks, and stacking interactions of the RNA to the binding pockets of the protein domains showed that binding is not sequence-specific and that many RNA fragments can bind to them successfully. Further calculations of the relative free energy of binding for different polypyrimidine sequences were carried out using the thermodynamic integration (TI) and single-step perturbation (SSP) methods. It is was not possible to calculate the relative free energies with high accuracy, but the obtained results do give qualitative insights into PTB's affinity for different RNA sequences. Furthermore, the low-energy conformations of the complexes that were found provided additional information about the mechanism of binding.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
0006-2960
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
5
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| pubmed:volume |
46
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
6500-12
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| pubmed:meshHeading |
pubmed-meshheading:17497933-Amino Acid Sequence,
pubmed-meshheading:17497933-Animals,
pubmed-meshheading:17497933-Computer Simulation,
pubmed-meshheading:17497933-Databases, Factual,
pubmed-meshheading:17497933-Gene Expression Regulation, Viral,
pubmed-meshheading:17497933-Humans,
pubmed-meshheading:17497933-Hydrogen Bonding,
pubmed-meshheading:17497933-Models, Molecular,
pubmed-meshheading:17497933-Molecular Conformation,
pubmed-meshheading:17497933-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:17497933-Peptide Chain Initiation, Translational,
pubmed-meshheading:17497933-Polypyrimidine Tract-Binding Protein,
pubmed-meshheading:17497933-Protein Binding,
pubmed-meshheading:17497933-Protein Structure, Tertiary,
pubmed-meshheading:17497933-RNA, Viral,
pubmed-meshheading:17497933-Thermodynamics
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| pubmed:year |
2007
|
| pubmed:articleTitle |
Mechanism and thermodynamics of binding of the polypyrimidine tract binding protein to RNA.
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| pubmed:affiliation |
Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH, CH-8093 Zürich, Switzerland.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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