Linked Life Data

19327364

Source:http://linkedlifedata.com/resource/pubmed/id/19327364

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-5-4
pubmed:abstractText
The transcription factor NF-kappaB (p50/p65) binds either a kappaB DNA element or its inhibitor protein, IkappaBalpha, but these two binding events are mutually exclusive. The reason for this exclusivity is not obvious from the available crystal structure data. The C-terminal PEST-like sequence of IkappaBalpha appears to be involved in the process, but it is located in both of the published X-ray structures of the IkappaBalpha/NF-kappaB complex at a significant distance away from the DNA contact loop in the NF-kappaB DNA-binding domain. We have used nuclear magnetic resonance spectroscopy and differential isotopic labeling to probe the interactions between the p50/p65 NF-kappaB heterodimer and IkappaBalpha in solution. Our measurements are able to resolve a local structural discrepancy between the two crystal structures, and we confirm that the primary interaction of the IkappaBalpha PEST domain is with the DNA-binding domain of the p65 subunit. Mutagenesis of key arginine residues in the DNA contact sequence results in the loss of specific interaction of the PEST sequence with the p65 subdomain. We conclude that the local structure of the IkappaBalpha/NF-kappaB complex in the region of the PEST sequence is consistent with a direct interaction of this acidic sequence with the basic DNA contact sequence in p65, thus reducing the affinity of NF-kappaB for DNA by a competitive mechanism that is still to be elucidated fully.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-10212987, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-10882738, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-10959627, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-11061227, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-11571291, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-15215520, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-15371334, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-16756995, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-16934999, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-17072321, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-17072323, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-17148610, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-18267068, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-18401342, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-18462667, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-18565540, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-18824506, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-2876518, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-3096580, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-7823953, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-7881273, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-7898917, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-8268157, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-8415639, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-8449662, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-8497253, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-8505309, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-8520220, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-8589602, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-8717528, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-8858144, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-9063887, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-9450761, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-9597130, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-9738011, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-9865689, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-9865693, http://linkedlifedata.com/resource/pubmed/commentcorrection/19327364-9865694
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1089-8638
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
388
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
824-38
pubmed:dateRevised
2011-3-24
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Interaction of the IkappaBalpha C-terminal PEST sequence with NF-kappaB: insights into the inhibition of NF-kappaB DNA binding by IkappaBalpha.
pubmed:affiliation
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural