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| {{STRUCTURE_1my7| PDB=1my7 | SCENE= }} | | {{STRUCTURE_1my7| PDB=1my7 | SCENE= }} |
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| '''NF-kappaB p65 subunit dimerization domain homodimer N202R mutation'''
| | ===NF-kappaB p65 subunit dimerization domain homodimer N202R mutation=== |
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| ==Overview==
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| IkappaBalpha inhibits transcription factor NF-kappaB activity by specific binding to NF-kappaB heterodimers composed of p65 and p50 subunits. It binds with slightly lower affinity to p65 homodimers and with significantly lower affinity to homodimers of p50. We have employed a structure-based mutagenesis approach coupled with protein-protein interaction assays to determine the source of this dimer selectivity exhibited by IkappaBalpha. Mutation of amino acid residues in IkappaBalpha that contact NF-kappaB only marginally affects complex binding affinity, indicating a lack of hot spots in NF-kappaB/IkappaBalpha complex formation. Conversion of the weak binding NF-kappaB p50 homodimer into a high affinity binding partner of IkappaBalpha requires transfer of both the NLS polypeptide and amino acid residues Asn202 and Ser203 from the NF-kappaB p65 subunit. Involvement of Asn202 and Ser203 in complex formation is surprising as these amino acid residues occupy solvent exposed positions at a distance of 20A from IkappaBalpha in the crystal structures. However, the same amino acid residue positions have been genetically isolated as determinants of binding specificity in a homologous system in Drosophila. X-ray crystallographic and solvent accessibility experiments suggest that these solvent-exposed amino acid residues contribute to NF-kappaB/IkappaBalpha complex formation by modulating the NF-kappaB p65 subunit NLS polypeptide.
| | The line below this paragraph, {{ABSTRACT_PUBMED_12460563}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12460563 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_12460563}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Phosphorylation]] | | [[Category: Phosphorylation]] |
| [[Category: Transcription regulation]] | | [[Category: Transcription regulation]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 01:51:49 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 23:36:06 2008'' |
