title: Induced alpha-helix structure in AF1 of the androgen receptor upon binding transcription factor TFIIF.
abstract: In recent years, it has become clear that in many proteins, significant regions are encoded by amino acid sequences that do not automatically fold into their fully condensed, functional structures. Characterization of the conformational propensities and function of the nonglobular protein sequences represents a major challenge. Striking among proteins with unfolded regions are numbers of transcription factors, including steroid receptors. In many cases, the unfolded or partially folded regions of such proteins take shape when the protein interacts with its proper binding partner(s), that is, the molecules to which it must bind to carry out its function. The AF1 domain of the androgen receptor (AR) shows little structure, when expressed as a recombinant peptide. It has been shown previously that AF1 interacts with transcription factor TFIIF in vitro. Using Fourier transform infrared (FTIR), we tested whether this interaction can induce structure in the AR AF1. Our results demonstrate that the recombinant AR AF1 can acquire significantly higher helical content after interacting with RAP74, a subunit of the TFIIF complex. We further show that this induced conformation in the AR AF1 is well-suited for its interaction with SRC-1.
authors.affiliation: Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555-1068, USA.
authors.forename: Raj
authors.initials: R
authors.lastname: Kumar
authors.forename: Russell
authors.initials: R
authors.lastname: Betney
authors.forename: Jianquan
authors.initials: J
authors.lastname: Li
authors.forename: E Brad
authors.initials: EB
authors.lastname: Thompson
authors.forename: Iain J
authors.initials: IJ
authors.lastname: McEwan
mesh_terms: D051548:Histone Acetyltransferases; D006801:Humans; D008744:Methylamines / Q000737:chemistry; D056920:Nuclear Receptor Coactivator 1; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000737:chemistry* / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D014157:Transcription Factors / Q000378:metabolism; D019473:Transcription Factors, TFII / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008744:Methylamines; D010446:Peptide Fragments; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D011994:Recombinant Proteins; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; C056604:transcription factor TFIIF; C005855:trimethyloxamine