The dimerization motif of cytosolic sulfotransferases

Cytosolic sulfotransferases sulfate steroids such as estrogens and hydroxys teroids. The enzymes, including human estrogen sulfotransferase (hEST) and hydroxysteroid sulfotransferase (hHST), are generally homodimers in solutio n with mouse estrogen sulfotransferase (mEST) being one of few exceptions. To identify the amino acid residues responsible for the dimerization, eight residues on the surface of hEST mere mutated to their counterparts in mEST and mutated hESTs were then analyzed by gel filtration chromatography. A s ingle mutation of Val(269) to Glu was sufficient to convert hEST to a monom er and the corresponding mutation of Val(260) also altered hHST to a monome r. The hHST crystal structure revealed a short stretch of peptide with the side-chains from two hHST monomers forming a hydrophobic zipper-like struct ure enforced by ion pairs at both ends. This peptide consisted of 10 residu es near the C-terminus that, including the critical Val residue, is conserv ed as KXXXTVXXXE in nearly all cytosolic sulfotransferases, When mEST under went the double mutations Pro269Thr/Glu270Val dimerization resulted. Thus, the KXXXTVXXXE sequence appears to be the common protein-protein interactio n motif that mediates the homo- as well as heterodimerization of cytosolic sulfotransferases. (C) 2001 Federation of European Biochemical Societies. P ublished by Elsevier Science B.V. All rights reserved.