Formation of the RFX gene regulatory complex induces folding of the interaction domain of RFXAP

Major Histocompatibility Complex Class II (MHCII) molecules have a central role in the mammalian adaptive immune response against infection. The level of the immune response is directly related to the concentration of MHCII molecules in the cell, which have a central role in initiating the immune response. MHCII molecules are therefore a potential target for the development of immunosuppressant drugs for the treatment of organ transplant rejection and autoimmune disease. The expression of MHCII molecules is regulated by a cell specific multi-protein complex termed the MHCII enhanceosome. The RFX complex is the key DNA binding component of the MHCII enhanceosome. The RFX complex is comprised of three proteins – RFX5, RFXAP, and RFXB – all of which are required for activation of expression of the MHCII genes. We have identified the precise regions of RFX5, RFXAP, and RFXB, that interact to form the RFX complex and have characterized the individual domains and the complexes they form. In addition, we have shown that the interaction between RFX5 and RFXAP promotes folding of RFXAP and this increases the affinity RFXAP has for RFXB.