Structure of NFAT1 bound as a dimer to the HIV-1 LTR kappa B element.
DNA binding by NFAT1 as a dimer has been implicated in the activation of host and viral genes. Here we report a crystal structure of NFAT1 bound cooperatively as a dimer to the highly conserved kappa B site from the human immunodeficiency virus 1 (HIV-1) long terminal repeat (LTR). This structure reveals a new mode of dimerization and protein-DNA recognition by the Rel homology region (RHR) of NFAT1. The two NFAT1 monomers form a complete circle around the kappa B DNA through protein-protein interactions mediated by both their N- and C-terminal subdomains. The major dimer interface, formed by the C-terminal domain, is asymmetric and substantially different from the symmetric dimer interface seen in other Rel family proteins. Comparison to other NFAT structures, including NFAT5 and the NFAT1-Fos-Jun-ARRE2 complex, reveals that NFAT1 adopts different conformations and its protein surfaces mediate distinct protein-protein interactions in the context of different DNA sites.
Giffin
Michael J
MJ
Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80309-0215, USA.
Stroud
James C
JC
Bates
Darren L
DL
von Koenig
Konstanze D
KD
Hardin
John
J
Chen
Lin
L
D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D016325:HIV Long Terminal Repeat / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors