The dimerization motif of cytosolic sulfotransferases

FEBS Letters

Borchers, Christoph H.¹  Petrotchenko, Evgeniy V.²  Pedersen, Lars C.²  Negishi, Masahiko²  Tomer, Kenneth B.¹ 

[1] Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA;Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA

关键词: Sulfotransferase;    Protein–protein interaction;    Mass spectrometry;    Crystal structure;    Site-directed mutagenesis;   

DOI  :  10.1016/S0014-5793(01)02129-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Cytosolic sulfotransferases sulfate steroids such as estrogens and hydroxysteroids. The enzymes, including human estrogen sulfotransferase (hEST) and hydroxysteroid sulfotransferase (hHST), are generally homodimers in solution 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 were mutated to their counterparts in mEST and mutated hESTs were then analyzed by gel filtration chromatography. A single mutation of Val²⁶⁹ to Glu was sufficient to convert hEST to a monomer and the corresponding mutation of Val²⁶⁰ also altered hHST to a monomer. The hHST crystal structure revealed a short stretch of peptide with the side-chains from two hHST monomers forming a hydrophobic zipper-like structure enforced by ion pairs at both ends. This peptide consisted of 10 residues near the C-terminus that, including the critical Val residue, is conserved as KXXXTVXXXE in nearly all cytosolic sulfotransferases. When mEST underwent the double mutations Pro269Thr/Glu270Val dimerization resulted. Thus, the KXXXTVXXXE sequence appears to be the common protein–protein interaction motif that mediates the homo- as well as heterodimerization of cytosolic sulfotransferases.

【 授权许可】

Unknown