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Molecular and Cellular Biology, March 2003, p. 2135-2150, Vol. 23, No. 6
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.6.2135-2150.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Electrostatic Modulation in Steroid Receptor Recruitment of LXXLL and FXXLF Motifs

Bin He and Elizabeth M. Wilson*

Laboratories for Reproductive Biology, Department of Biochemistry and Biophysics, and Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599-7500

Received 24 July 2002/ Returned for modification 3 December 2002/ Accepted 20 December 2002

Coactivator recruitment by activation function 2 (AF2) in the steroid receptor ligand binding domain takes place through binding of an LXXLL amphipathic {alpha}-helical motif at the AF2 hydrophobic surface. The androgen receptor (AR) and certain AR coregulators are distinguished by an FXXLF motif that interacts selectively with the AR AF2 site. Here we show that LXXLL and FXXLF motif interactions with steroid receptors are modulated by oppositely charged residues flanking the motifs and charge clusters bordering AF2 in the ligand binding domain. An increased number of charged residues flanking AF2 in the ligand binding domain complement the two previously characterized charge clamp residues in coactivator recruitment. The data suggest a model whereby coactivator recruitment to the receptor AF2 surface is initiated by complementary charge interactions that reflect a reversal of the acidic activation domain-coactivator interaction model.

* Corresponding author. Mailing address: CB# 7500, Rm. 374 Medical Sciences Research Building, University of North Carolina, Chapel Hill, NC 27599. Phone: (919) 966-5168. Fax: (919) 966-2203. E-mail: emw{at}med.unc.edu.

Molecular and Cellular Biology, March 2003, p. 2135-2150, Vol. 23, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.6.2135-2150.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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