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Proteins DOI:10.1002/prot.22379

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

Publication TypeJournal Article
Year of Publication2009
AuthorsBriggs, LT, Laird, K, Boss, JM, Garvie, CW
Date Published2009 Aug 15
KeywordsCalorimetry, Circular Dichroism, DNA-Binding Proteins, Gene Expression Regulation, Genetic Vectors, Humans, Magnetic Resonance Spectroscopy, Mutagenesis, Site-Directed, Polymerase Chain Reaction, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Regulatory Factor X Transcription Factors, Transcription Factors

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 multiprotein complex. The RFX complex is the key DNA binding component of this complex. The RFX complex is composed of three proteins-RFX5, RFXAP, and RFXB-all of which are required for activation of expression of the MHCII genes. Little is currently known about the precise regions of the RFX proteins that are required for complex formation, or their structure. We have therefore identified the key regions of RFX5, RFXAP, and RFXB, which are required to form the RFX complex and have characterized the individual domains and the complexes they form using NMR and circular dichroism spectroscopy and isothermal titration calorimetry. Our results support a model for the assembly of the RFX complex in which the interaction between RFX5 and RFXAP promote folding of a poorly structured region ofRFXAP, which is required for high affinity binding of RFXB to the RFX5.RFXAP complex.


Alternate JournalProteins
PubMed ID19274739
PubMed Central IDPMC2700855
Grant ListR01 GM047310-13 / GM / NIGMS NIH HHS / United States
R25-GM55036 / GM / NIGMS NIH HHS / United States
R25 GM055036 / GM / NIGMS NIH HHS / United States
R01 AI034000-14 / AI / NIAID NIH HHS / United States
R01 GM047310 / GM / NIGMS NIH HHS / United States
R01 AI034000 / AI / NIAID NIH HHS / United States