Linked Life Data

19505151

Source:http://linkedlifedata.com/resource/pubmed/id/19505151

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2009-6-30
pubmed:abstractText
The tumor suppressor protein p53 is a nuclear protein that serves as an important transcription factor. The region responsible for sequence-specific DNA interaction is located in its core domain (p53C). Although full-length p53 binds to DNA as a tetramer, p53C binds as a monomer since it lacks the oligomerization domain. It has been previously demonstrated that two core domains have a dimerization interface and undergo conformational change when bound to DNA. Here we demonstrate that the interaction with a consensus DNA sequence provides the core domain of p53 with enhanced conformational stability at physiological salt concentrations (0.15 M). This stability could be either increased or abolished at low (0.01 M) or high (0.3 M) salt concentrations, respectively. In addition, interaction with the cognate sequence prevents aggregation of p53C into an amyloid-like structure, whereas binding to a nonconsensus DNA sequence has no effect on p53C stability, even at low ionic strength. Strikingly, sequence-specific DNA binding also resulted in a large stabilization of full-length p53, whereas nonspecific sequence binding led to no stabilization. The effects of cognate DNA could be mimicked by high concentrations of osmolytes such as glycerol, which implies that the stabilization is caused by the exclusion of water. Taken together, our results show an enhancement in protein stability driven by specific DNA recognition. When cognate DNA was added to misfolded protein obtained after a pressurization cycle, the original conformation was mostly recovered. Our results may aid the development of therapeutic approaches to prevent misfolded species of p53.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6126-35
pubmed:meshHeading
pubmed-meshheading:19505151-Anilino Naphthalenesulfonates, pubmed-meshheading:19505151-Consensus Sequence, pubmed-meshheading:19505151-DNA, pubmed-meshheading:19505151-Fluorescent Dyes, pubmed-meshheading:19505151-Glycerol, pubmed-meshheading:19505151-Humans, pubmed-meshheading:19505151-Hydrostatic Pressure, pubmed-meshheading:19505151-Light, pubmed-meshheading:19505151-Osmolar Concentration, pubmed-meshheading:19505151-Polydeoxyribonucleotides, pubmed-meshheading:19505151-Protein Binding, pubmed-meshheading:19505151-Protein Conformation, pubmed-meshheading:19505151-Protein Denaturation, pubmed-meshheading:19505151-Protein Folding, pubmed-meshheading:19505151-Protein Stability, pubmed-meshheading:19505151-Recombinant Proteins, pubmed-meshheading:19505151-Scattering, Radiation, pubmed-meshheading:19505151-Spectrometry, Fluorescence, pubmed-meshheading:19505151-Tumor Suppressor Protein p53, pubmed-meshheading:19505151-Water
pubmed:year
2009
pubmed:articleTitle
Cognate DNA stabilizes the tumor suppressor p53 and prevents misfolding and aggregation.
pubmed:affiliation
Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't