The activation domains of many transcription factors appear to exist naturally in an unfolded or only partially folded state. This seems to be the case for AF1/tau1, the major transactivation domain of the human glucocorticoid receptor. We show here that in buffers containing the natural osmolyte trimethylamineN-oxide (TMAO), recombinant AF1 folds into more a compact structure, as evidenced by altered fluorescence emission, circular dichroism spectra, and ultracentrifugal analysis. This conformational transition is cooperative, a characteristic of proteins folding to natural structures. The structure resulting from incubation in TMAO causes the peptide to resist proteolysis by trypsin, chymotrypsin, endoproteinase Arg-C and endoproteinase Gluc-C. Ultracentrifugation studies indicate that AF1/tau1 exists as a monomer in aqueous solution and that the presence of TMAO does not lead to oligomerization or aggregation. It has been suggested that recombinant AF1 binds both the ubiquitous coactivator CBP and the TATA box-binding protein, TBP. Interactions with both of these are greatly enhanced in the presence of TMAO. Co-immunoadsorption experiments indicate that in TMAO each of these and the coactivator SRC-1 are found complexed with AF1. These data indicate that TMAO induces a conformation in AF1/tau1 that is important for its interaction with certain co-regulatory proteins. The activation domains of many transcription factors appear to exist naturally in an unfolded or only partially folded state. This seems to be the case for AF1/tau1, the major transactivation domain of the human glucocorticoid receptor. We show here that in buffers containing the natural osmolyte trimethylamineN-oxide (TMAO), recombinant AF1 folds into more a compact structure, as evidenced by altered fluorescence emission, circular dichroism spectra, and ultracentrifugal analysis. This conformational transition is cooperative, a characteristic of proteins folding to natural structures. The structure resulting from incubation in TMAO causes the peptide to resist proteolysis by trypsin, chymotrypsin, endoproteinase Arg-C and endoproteinase Gluc-C. Ultracentrifugation studies indicate that AF1/tau1 exists as a monomer in aqueous solution and that the presence of TMAO does not lead to oligomerization or aggregation. It has been suggested that recombinant AF1 binds both the ubiquitous coactivator CBP and the TATA box-binding protein, TBP. Interactions with both of these are greatly enhanced in the presence of TMAO. Co-immunoadsorption experiments indicate that in TMAO each of these and the coactivator SRC-1 are found complexed with AF1. These data indicate that TMAO induces a conformation in AF1/tau1 that is important for its interaction with certain co-regulatory proteins. glucocorticoid receptor human GR trimethylamine N-oxide ligand-binding domain DNA-binding domain TATA box-binding protein glutathione S-transferase endoproteinase polyacrylamide gel electrophoresis polyvinylidene difluoride Transcriptional activation by the glucocorticoid receptor (GR)1 is mediated through the function of three regions in the protein, AF1/tau1, tau2, and AF2. Numerous mutational analyses have shown that of these, AF1/tau1 makes by far the largest quantitative contribution to transcriptional activation. Deletion or inactivating mutations of AF1/tau1 reduce the ability of the GR to activate transcription from test genes by at least 60–70% (1Dahlman-Wright K. Almlof T. McEwan I.J. Gustafsson J.A. Wright A.P.H. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 1619-1923Crossref PubMed Scopus (84) Google Scholar, 2Giguere V. Hollenberg S.M. Rosenfeld M.G. Evans R.M. Cell. 1986; 46: 645-652Abstract Full Text PDF PubMed Scopus (672) Google Scholar, 3Hollenberg S.M. Evans R.M. Cell. 1988; 55: 899-906Abstract Full Text PDF PubMed Scopus (545) Google Scholar). As defined by molecular genetic analyses, tau2 and AF2 are located in the C-terminal ligand-binding domain (LBD) of the receptor, whereas AF1/tau1 lies N-terminal from the centrally located DNA-binding domain (DBD). In the human GR (hGR) AF1 is encompassed by amino acids 77–262 (3Hollenberg S.M. Evans R.M. Cell. 1988; 55: 899-906Abstract Full Text PDF PubMed Scopus (545) Google Scholar). Precisely how the AF1/tau1 transactivation region functions is unknown, in part due to lack of knowledge of its working structure; yet this structure must provide the basis for essential, specific interactions with other proteins. Studies undertaken in our laboratory and others (4Dahlman-Wright K. Baumannm H. McEwan I.J. Almlof T. Wright A.P.H. Gustafsson J.A. Hard T. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 1699-1703Crossref PubMed Scopus (137) Google Scholar, 5Baskakov I.V. Kumar R. Srinivasan G. Ji Y. Bolen D.W. Thompson E.B. J. Biol. Chem. 1999; 274: 10693-10696Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar) have shown that when expressed independently in dilute aqueous solutions, AF1 appears to have little structure. Instead it appears to exist as a collection of conformers that overall appears as random coil. However, in the presence of the strong α-helix stabilizing agent trifluoroethanol, as many as three segments toward the C-terminal end of the AF1/tau1 region exhibit α-helical characteristics (4Dahlman-Wright K. Baumannm H. McEwan I.J. Almlof T. Wright A.P.H. Gustafsson J.A. Hard T. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 1699-1703Crossref PubMed Scopus (137) Google Scholar). Mutations in the GR tau1/AF1 transactivation region coupled with assays of function have suggested that this ability to form α-helical conformation in vitrocorrelates with the transactivation potential of the region (4Dahlman-Wright K. Baumannm H. McEwan I.J. Almlof T. Wright A.P.H. Gustafsson J.A. Hard T. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 1699-1703Crossref PubMed Scopus (137) Google Scholar). The subdomain of AF1/tau1 that subsumes the potential helices has been referred to as the AF1 core (AF1c), and when this core is expressed separately while connected to an exogenous DNA-binding domain, AF1 retains considerable transactivating activity. Mutations of acidic amino acids in AF1, including the core, had little effect on such activity; however, mutations altering several hydrophobic residues of AF1/tau1 significantly diminished its transcriptional activation potential (6Almlof T. Gustafsson J.A. Wright A.P.H. Biochemistry. 1998; 37: 9586-9594Crossref PubMed Scopus (71) Google Scholar). In recent years, a number of proteins that modulate GR activity, such as GRIP1, RIP140, SRC-1, and CBP/p300, have been identified (7McKenna J. Lanz B. O'Malley B.W. Endocr. Rev. 1999; 20: 321-344Crossref PubMed Scopus (1629) Google Scholar, 8Glass C.K. Rose D.W. Rosenfeld M.G. Curr. Opin. Cell Biol. 1997; 9: 222-232Crossref PubMed Scopus (599) Google Scholar, 9Horwitz K.B. Jackson T.A. Bain D.L. Richer J.K. Takimoto G.S. Tung L. Mol. Endocrinol. 1996; 10: 1167-1177Crossref PubMed Scopus (830) Google Scholar). These co-regulators bind the GR and presumably act as molecular bridges to the primary transcriptional machinery. Most co-regulators have been identified through their ligand-dependent interactions with the LBD, in particular, with the AF2 domain in members of the receptor family of which the GR is part (10McEwan I.J. Wright A.P.H. Gustafsson J.A. BioEssays. 1997; 19: 153-160Crossref PubMed Scopus (159) Google Scholar, 11Hong H. Kohli K. Trivedi A. Johnson D.L. Stallcup M.R. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 4948-4952Crossref PubMed Scopus (610) Google Scholar, 12Cavailles V. Dauvois S.S. L'Horset F. Lopez G. Hoare S. Kushner P.J. Parker M.G. EMBO J. 1995; 14: 3741-3751Crossref PubMed Scopus (670) Google Scholar, 13Onate S.A. Tsai S.Y. Tsai M.J. O'Malley B.W. Science. 1995; 270: 1354-1357Crossref PubMed Scopus (2039) Google Scholar, 14Chrivia J.C. Kwok R.P. Lamb N. Hagiwara M. Montminy M.R. Goodman R.H. Nature. 1993; 365: 855-859Crossref PubMed Scopus (1755) Google Scholar). However, it is not known whether the co-regulators function exclusively through this part of the GR or whether they can also modulate the activity of CBP and several other co-regulators have been shown to not to recombinant AF1/tau1 A. Almlof T. J. McEwan I.J. Gustafsson J.A. Wright A.P.H. Mol. Cell. Biol. 1997; PubMed Scopus Google Scholar, J. McEwan I.J. Wright Gustafsson J.A. Mol. Endocrinol. 1997; Scopus Google Scholar, A. Gustafsson J.A. Wright A.P.H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). recent or the potential helices connected to a GR DNA-binding domain in a with a of CBP to activate A. Gustafsson J.A. Wright A.P.H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). AF1 has also been shown to bind J. McEwan I.J. Wright Gustafsson J.A. Mol. Endocrinol. 1997; Scopus Google the TATA box-binding protein that the basis for the transcription This the that the AF1 GR domain the transcription machinery. In transcription studies that the to the S.Y. Srinivasan G. Thompson E.B. O'Malley B.W. J. Biol. Chem. Full Text PDF PubMed Google Scholar). is that a conformation of AF1/tau1 is or its interaction with specific proteins. This in has been for the activation domains of transcription factors I.J. K. J. Wright A.P.H. Biochemistry. 1996; PubMed Scopus Google F. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). data of the that folding of the AF1/tau1 region is an important for its interaction with factors and in In the of AF1/tau1 for transcriptional activation presumably is or by from and of factors and the conformation by AF1/tau1 lead to of the of this region in the transcription to how or have been to the as to proteins into Biochemistry. PubMed Scopus Google Scholar, Science. PubMed Scopus Google Scholar, J. 1995; PubMed Google Scholar, J.C. J. Biol. Chem. Full Text PDF PubMed Google Scholar, Y. Bolen D.W. Biochemistry. 1995; PubMed Scopus Google Scholar, Y. Bolen Bolen D.W. Proc. Natl. Acad. Sci. U. S. A. 1998; PubMed Scopus Google Scholar). such trimethylamine N-oxide (TMAO), has been to proteins into proteins with activity I.V. Bolen D.W. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar, I.V. Bolen D.W. J. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). We that TMAO induces and structure in a GR containing the the acids The conformational transition of this GR is in I.V. Kumar R. Srinivasan G. Ji Y. Bolen D.W. Thompson E.B. J. Biol. Chem. 1999; 274: 10693-10696Abstract Full Text Full Text PDF PubMed Scopus (147) Google a characteristic of proteins folding to their of the in this GR appear to be in the N-terminal domain, that TMAO induces an conformation in the AF1/tau1 and this conformation is important for its interaction with proteins. In this studies of the conformation in the AF1/tau1 region expressed data that TMAO induces and structure in the AF1/tau1 and this conformation greatly its interaction with certain co-regulatory proteins and TBP. and of AF1/tau1 has been I.V. Kumar R. Srinivasan G. Ji Y. Bolen D.W. Thompson E.B. J. Biol. Chem. 1999; 274: 10693-10696Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar). The containing the recombinant for with for and The a at AF1/tau1 protein from the by by a as I.V. Kumar R. Srinivasan G. Ji Y. Bolen D.W. Thompson E.B. J. Biol. Chem. 1999; 274: 10693-10696Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar). or protein by the protein by gel electrophoresis with and to be of AF1/tau1 protein in solution at of TMAO. The a at of or as I.V. Kumar R. Srinivasan G. Ji Y. Bolen D.W. Thompson E.B. J. Biol. Chem. 1999; 274: 10693-10696Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar). in at and the data for the contribution of the of protein at a of as in containing TMAO. The at on an a with the of and of The at a protein of the presence and of in and for the contribution of shown is a of and trypsin, chymotrypsin, endoproteinase and endoproteinase Arg-C for with of AF1/tau1 in for which at for other at for and Arg-C at a of whereas and at by and the in a The on gel and by protein the in in the presence and of TMAO. gel the proteins The largest in the containing TMAO and by of J. Biol. Chem. Full Text PDF PubMed Google Scholar). with a a AF1/tau1 protein in a containing with at The the of the PubMed Scopus Google Scholar) as by J. Biochemistry. Scholar) to to and The for which for with and a studies the at and The to be at when in the of least the Scopus Google Scholar, J. Full Text PDF PubMed Scopus Google Scholar). The the as in protein in a containing with or TMAO on from and to the to the and the for protein The of TMAO the the and the for in a on a gel and by CBP CBP expressed in as H. Srinivasan G. Thompson E.B. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google and this in of other gel proteins a The by incubation for at in containing proteins and at with The and by AF1/tau1 and proteins in a containing or to a of and for at of or and of and for by and The in and for gel the proteins a and an amino acids of the human GR as As with other the GR several major These are shown for the human GR in The AF1/tau1 transactivation amino acids 77–262 is with the the of the and residues This domain expressed in a as a protein at the N-terminal with glutathione S-transferase the the folding of the AF1/tau1 to the the and The fluorescence of recombinant AF1/tau1 are in a the in the and presence of TMAO at which the both from and the fluorescence at which in the of the located the potential helices of the AF1 In both of spectra, the of the fluorescence is in the presence of with an of at TMAO. are in the in the presence of TMAO. These fluorescence are of the of residues from aqueous solution into a more hydrophobic the the in and the in fluorescence indicate the of compact structure in the presence of TMAO. the three amino acids are located in AF1/tau1, the conformational in the fluorescence be the TMAO induces this conformational transition in AF1/tau1 in a as shown by the in fluorescence at as a function of TMAO These that TMAO folds AF1/tau1 region into a more compact structure, and the of the is a of protein folding Rose Sci. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, M. J. Mol. Biol. 1998; PubMed Scopus Google of AF1/tau1 in the and presence TMAO. The and the in the and presence of TMAO. in in a at and at and show the conformational transition of AF1/tau1 by as by in at with to of TMAO. The in in containing in the with The least of data to the of protein Bolen D.W. Biochemistry. 1988; PubMed Scopus Google Scholar) of in and in the studies a containing the fluorescence in this to whether the in AF1/tau1 TMAO at this In and the of the fluorescence is significantly TMAO as in and the in at is significantly with that at that the conformational transition of folding of AF1/tau1 by TMAO. The conformational transition in AF1/tau1 in also is and at with that of in These fluorescence studies indicate that the conformational transition in AF1/tau1 is more at The fluorescence of AF1/tau1 in the presence and of TMAO that TMAO causes structure to form in this for structure in AF1/tau1, the of this protein in the presence and of TMAO of the that in the presence of the at is significantly of the These data the that TMAO causes structure to in the As of the in the structure of the AF1/tau1 region by of the protein with in the presence and of the be that the not with activity, activity on the activity not by TMAO. In proteolysis of the test due to the osmolyte the natural conformation of the not The of of AF1/tau1 by and are shown in It is that the as the of TMAO and the protein is by both and and whereas it is partially at and TMAO and and or TMAO AF1/tau1 appears to be that it has folded into a structure that the residues by these to not by when AF1/tau1 with the and Arg-C in the case of the not as In the case of only at TMAO. We the peptide resulting from of and AF1/tau1, to whether the form folded regions to The data in with lack of structure in recombinant We the peptide of the folded by TMAO. to each of the both and AF1/tau1 show incubation in the presence of TMAO for to not The of at in the presence of TMAO that TMAO can in AF1/tau1 whether it is or TMAO is to the recombinant protein domain into a structure not in this from that by the These that in a of AF1/tau1 folds to a and that it in this of the of TMAO of the of AF1 in the presence of TMAO identified by their In the of these in the AF1/tau1 domain are shown region at the of AF1/tau1 from by trypsin, chymotrypsin, and Gluc-C. potential for these exist that three in a region amino not by as the of these three that in TMAO a of AF1/tau1 amino is to by which has only potential in The is This is with the that in the a region amino is to It is from these that structure in AF1/tau1 is not to only part of the It is from our data that TMAO to the of a of and structure in the The in the presence of TMAO from an oligomerization of the protein by the presence of the studies to the of TMAO on the structure of the from studies of AF1/tau1 in the and presence of TMAO found to a as shown in and the of protein in the for in that The for AF1/tau1 in the presence of TMAO is which to the for a protein of of for the Scholar). However, the for AF1/tau1 in TMAO is with that of a protein of the molecular that an or an experiments also at three and The the presence of a protein of a molecular of which to the molecular for these studies indicate that to AF1/tau1 exists as a monomer in the aqueous in this and that to TMAO does not protein aggregation. It is that AF1/tau1 makes interactions with other factors in to J. McEwan I.J. Wright Gustafsson J.A. Mol. Endocrinol. 1997; Scopus Google Scholar) and that folding is important for these interactions (6Almlof T. Gustafsson J.A. Wright A.P.H. Biochemistry. 1998; 37: 9586-9594Crossref PubMed Scopus (71) Google Scholar). We whether the conformation in AF1/tau1 by TMAO is important for specific a with to as the that in the presence of several proteins from an of the It is from the gel that when TMAO is binds only certain proteins from molecular that are not in the in the and molecular that is in the is on the or in of TMAO not these proteins. experiments both and proteins the that in TMAO certain proteins have for In the the proteins to the on in the presence of the with proteins with a containing TMAO. and electrophoresis of the proteins that of TMAO from the had not these proteins from the that the AF1/tau1 in the presence of they and to specific AF1/tau1 the proteins by these with a of known RIP140, SRC-1 have been shown to with to transcriptional activation (7McKenna J. Lanz B. O'Malley B.W. Endocr. Rev. 1999; 20: 321-344Crossref PubMed Scopus (1629) Google Scholar, 8Glass C.K. Rose D.W. Rosenfeld M.G. Curr. Opin. Cell Biol. 1997; 9: 222-232Crossref PubMed Scopus (599) Google Scholar, 9Horwitz K.B. Jackson T.A. Bain D.L. Richer J.K. Takimoto G.S. Tung L. Mol. Endocrinol. 1996; 10: 1167-1177Crossref PubMed Scopus (830) Google Scholar, I.J. Wright A.P.H. Gustafsson J.A. BioEssays. 1997; 19: 153-160Crossref PubMed Scopus (159) Google Scholar, 11Hong H. Kohli K. Trivedi A. Johnson D.L. Stallcup M.R. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 4948-4952Crossref PubMed Scopus (610) Google Scholar, 12Cavailles V. Dauvois S.S. L'Horset F. Lopez G. Hoare S. Kushner P.J. Parker M.G. EMBO J. 1995; 14: 3741-3751Crossref PubMed Scopus (670) Google Scholar, 13Onate S.A. Tsai S.Y. Tsai M.J. O'Malley B.W. Science. 1995; 270: 1354-1357Crossref PubMed Scopus (2039) Google Scholar, 14Chrivia J.C. Kwok R.P. Lamb N. Hagiwara M. Montminy M.R. Goodman R.H. Nature. 1993; 365: 855-859Crossref PubMed Scopus (1755) Google Scholar). with the for GRIP1, RIP140, or in the presence or of TMAO. such is shown in with (6Almlof T. Gustafsson J.A. Wright A.P.H. Biochemistry. 1998; 37: 9586-9594Crossref PubMed Scopus (71) Google in the of TMAO a interaction with and This in the presence of TMAO In the of TMAO the not a in the proteins show a with a protein of in a at and a strong at whether TMAO enhanced an interaction CBP and AF1/tau1, with a CBP to CBP In from these found that in the presence of TMAO a protein of to the by the the other proteins in the presence of TMAO on the TBP. a TMAO these AF1/tau1 CBP and primary in that had been with recombinant We also for proteins with an to the protein the to with each the protein by to The and the proteins and by electrophoresis in on polyacrylamide to amino acids of the to In the of a of AF1 found to have been on the with and interaction TMAO. In the presence of a strong interaction of AF1 with each of the other proteins has been shown to have these interaction data indicate that folding in AF1/tau1 is important for its interaction with these be and Deletion studies have that the AF1/tau1 transactivation region retains only a of its transactivation activity (1Dahlman-Wright K. Almlof T. McEwan I.J. Gustafsson J.A. Wright A.P.H. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: 1619-1923Crossref PubMed Scopus (84) Google Scholar, 2Giguere V. Hollenberg S.M. Rosenfeld M.G. Evans R.M. Cell. 1986; 46: 645-652Abstract Full Text PDF PubMed Scopus (672) Google it has been that this region a major in by It has been that AF1/tau1 makes with certain other proteins to activate genes (6Almlof T. Gustafsson J.A. Wright A.P.H. Biochemistry. 1998; 37: 9586-9594Crossref PubMed Scopus (71) Google Scholar, A. Almlof T. J. McEwan I.J. Gustafsson J.A. Wright A.P.H. Mol. Cell. Biol. 1997; PubMed Scopus Google Scholar, J. McEwan I.J. Wright Gustafsson J.A. Mol. Endocrinol. 1997; Scopus Google Scholar, A. Gustafsson J.A. Wright A.P.H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). It has also been shown that a C-terminal of AF1/tau1 is for its transactivation activity. This region has a to form and in the presence of trifluoroethanol, it can form three segments (4Dahlman-Wright K. Baumannm H. McEwan I.J. Almlof T. Wright A.P.H. Gustafsson J.A. Hard T. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 1699-1703Crossref PubMed Scopus (137) Google Scholar). These potential helices important for interactions with a of CBP in a A. Gustafsson J.A. Wright A.P.H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The of folding that the AF1/tau1 region is in it a more conformation R. T. Cell. 1994; Full Text PDF PubMed Scopus Google Scholar). In this have the folding of recombinant AF1/tau1 in the presence of a naturally which has been shown to proteins into I.V. Bolen D.W. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). that TMAO causes a of structure to form in the AF1/tau1 The fluorescence data indicate a of hydrophobic amino acids into a more the of as natural hydrophobic protein In both and the conformational transition is cooperative, a of naturally folding proteins Rose Sci. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, M. J. Mol. Biol. 1998; PubMed Scopus Google and the is to that folding of proteins. of protein folding is in a in J. 1995; PubMed Google Scholar). to its effect on the peptide Y. Bolen D.W. Biochemistry. 1995; PubMed Scopus Google TMAO proteins to to altering the for folding Y. Bolen D.W. Biochemistry. 1995; PubMed Scopus Google Scholar). including this in a of on these and on our it is that TMAO folding to a natural structure in The and the fluorescence data both to this These data that the and residues to more hydrophobic to the of the The a in molecular that the protein is more and a structure in the presence of this the of the shown in is to the of the protein, the in the for AF1/tau1 in the presence of TMAO a for the molecular protein that the of the protein is more compact or the data are in with the that the presence of TMAO induces AF1/tau1 to a more of The data from with of in the indicate that regions of AF1 are that of the recombinant peptide is on these that an conformation or of in AF1/tau1 in for it to its transcription This by an in which AF1/tau1 as the of interaction with its or by a in the a of the form and a of form In the the of can interactions with the to TMAO the interaction of AF1/tau1 with its in the AF1/tau1 be partially data on domain of the GR R. I.V. Srinivasan G. Bolen D.W. J.C. Thompson E.B. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar) and the data of others D.L. Takimoto G.S. K.B. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) on the receptor and its N-terminal region are with data in the that AF1/tau1 is a TMAO causes AF1 to a structure, the interaction of the domain with proteins be It is that AF1/tau1 makes a with or other proteins to activate It has been shown that the AF1/tau1 core can bind to several proteins important for including CBP and (6Almlof T. Gustafsson J.A. Wright A.P.H. Biochemistry. 1998; 37: 9586-9594Crossref PubMed Scopus (71) Google Scholar, A. Almlof T. J. McEwan I.J. Gustafsson J.A. Wright A.P.H. Mol. Cell. Biol. 1997; PubMed Scopus Google Scholar, J. McEwan I.J. Wright Gustafsson J.A. Mol. Endocrinol. 1997; Scopus Google Scholar, A. Gustafsson J.A. Wright A.P.H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). These proteins have also been to with the of the presumably at AF2. of the data for the AF1/tau1 interactions with these proteins that only a of be This is with the of our in which a of AF1/tau1 is in the folded of such whereas of AF1/tau1 unfolded due to the of interaction experiments show that in the of AF1/tau1 to a number of other proteins is greatly the interactions of AF1 with and SRC-1 are enhanced in the presence of TMAO. our that TMAO folds the conformers of AF1/tau1 into a conformation which is for its interaction with other AF1/tau1 this or TATA box-binding can with this part of the receptor and its structure. We have our assays that the factors of TMAO does not this not on presence of TMAO. it can be that TMAO a conformation of AF1/tau1, and proteins this structure. We have also data that an containing the to its DNA-binding causes AF1 to R. I.V. Srinivasan G. Bolen D.W. J.C. Thompson E.B. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). a in which the data for AF1/tau1 are in the of This the that interactions the proteins at AF1 and other of the AF2. that GR AF1 and AF2 in with each other through the J.A. M.J. EMBO J. 1999; PubMed Scopus Google Scholar). from other factors such as to glucocorticoid or also a We and the of the of for their in and the AF1/tau1 We also for and for and for in the The by a The CBP by of
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