Crystal structure of NF-κb (p50)2 complexed to a high-affinity RNA aptamer

De Bin Huang, Don Vu, Laura A. Cassiday, Jeff M. Zimmerman, L James Maher III, Gourisankar Ghosh

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

We have recently identified an RNA aptamer for the transcription factor NF-κB p50 homodimer [(p50)2], which exhibits little sequence resemblance to the consensus DNA target for (p50)2, but binds (p50)2 with an affinity similar to that of the optimal DNA target. We describe here the 2.45-Å resolution x-ray crystal structure of the p50 RHR/RNA aptamer complex. The structure reveals that two RNA molecules bind independent of each other to the p50 N-terminal Ig-like domains. The RNA secondary structure is comprised of a stem and a stem-loop separated by an internal loop folded into a kinked helix because of the cross-strand stacking of three internal loop guanines. These guanines, placed at the edge of the 3′ helix, together with the major groove of the irregular 3′ helix, form the binding surface for p50. Each p50 monomer uses the same surface to recognize the distorted RNA major groove as observed in the κB DNA/p50 RHR complex, resulting in strikingly similar interfaces. The structure reveals how the aptamer specifically selects p50 and discriminates against p65. We also discuss the physiological implications of RNA binding by (p50)2.

Original languageEnglish (US)
Pages (from-to)9268-9273
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number16
DOIs
StatePublished - Aug 5 2003

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Nucleotide Aptamers
RNA
Guanine
DNA
Transcription Factors
X-Rays

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Crystal structure of NF-κb (p50)2 complexed to a high-affinity RNA aptamer. / Huang, De Bin; Vu, Don; Cassiday, Laura A.; Zimmerman, Jeff M.; Maher III, L James; Ghosh, Gourisankar.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 16, 05.08.2003, p. 9268-9273.

Research output: Contribution to journalArticle

Huang, De Bin ; Vu, Don ; Cassiday, Laura A. ; Zimmerman, Jeff M. ; Maher III, L James ; Ghosh, Gourisankar. / Crystal structure of NF-κb (p50)2 complexed to a high-affinity RNA aptamer. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 16. pp. 9268-9273.
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