1MY7

NF-kappaB p65 subunit dimerization domain homodimer N202R mutation

Summary for 1MY7

• Entry DOI: 10.2210/pdb1my7/pdb
• Related: 1bft 1my5
• Descriptor: NF-kappaB p65 (RelA) subunit (2 entities in total)
• Functional Keywords: immunoglobulin, ig, beta-sandwich, beta-sheet, homodimerdna-binding, transcription regulation, activator, nuclear protein, phosphorylation, transcription
• Biological source: Mus musculus (house mouse)
• Cellular location: Nucleus: Q04207
• Total number of polymer chains: 2
• Total formula weight: 26489.94

Authors

Huxford, T.,Mishler, D.,Phelps, C.B.,Huang, D.-B.,Sengchanthalangsy, L.L.,Reeves, R.,Hughes, C.A.,Komives, E.A.,Ghosh, G. (deposition date: 2002-10-03, release date: 2002-12-04, Last modification date: 2024-02-14)

Primary citation

Huxford, T.,Mishler, D.,Phelps, C.B.,Huang, D.-B.,Sengchanthalangsy, L.L.,Reeves, R.,Hughes, C.A.,Komives, E.A.,Ghosh, G.
Solvent exposed non-contacting amino acids play a critical role in NF-kappaB/IkappaB alpha complex formation
J.Mol.Biol., 324:587-597, 2002

PubMed Abstract: 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.

PubMed: 12460563
DOI: 10.1016/S0022-2836(02)01149-X

Experimental method

X-RAY DIFFRACTION (1.49 Å)