This group represents the DNA-binding protein RFXANK which activates transcription from class II MHC promoters, requiring the activity of the MHC class II transactivator/CIITA. Deficiency is the commonest cause of bare lymphocyte syndrome (the absence of MHC class II transcription and humoral- and cellular-mediated immune responses to foreign antigens) [, ].
This superfamily represents the C-terminal domain ofRFXAP (regulatory factor X-associated protein) that binds to RFXANK [, ], the ankyrin-repeat regulatory factor X protein. RFXAP is part of the RFX complex, mutants of either RFXAP or RFXANK protein fail to bind to each other. RFX5 binds only to the RFXANK-RFXAP scaffold and not to either protein alone, and neither the scaffold nor RFX5 alone can bind DNA. The binding of the RFXANK-RFXAP scaffold to RFX5 leads to a conformational change in the latter that exposes the DNA-binding domain of RFX5. The DNA-binding domain of RFX5 anchors the RFX complex to MHC class II X and S promoter boxes [].
This C-terminal domain of Regulatory factor X-associated protein (RFXAP) binds to RFXANK [, ], the ankyrin-repeat regulatory factor X protein. RFXAP is part of the RFX complex, mutants of either RFXAP or RFXANK protein fail to bind to each other. RFX5 binds only to the RFXANK-RFXAP scaffold and not to either protein alone, and neither the scaffold nor RFX5 alone can bind DNA. The binding of the RFXANK-RFXAP scaffold to RFX5 leads to a conformational change in the latter that exposes the DNA-binding domain of RFX5. The DNA-binding domain of RFX5 anchors the RFX complex to MHC class II X and S promoter boxes [].
Transcription of all the members of MHCII family of genes is controlled by a set of conserved transcription factors and promoter elements. One of these class II transactivators is the DNA-binding RFX complex, which consists of subunits RFX5 and its accessory proteins RFXAP and RFXANK [].This entry represents the C-terminal domain of RFX5. The C-terminal domain mediates cooperative binding between the RFX complex and NF-Y, a transcription factor binding to the Y box sequence of MHC-II promoters [].
