Reversible Oxidation of the Membrane Distal Domain of Receptor PTP Is Mediated by a Cyclic Sulfenamide
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- 作者：Jing Yang ; Arnoud Groen ; Simone Lemeer ; Anne Jans ; Monique Slijper ; S. Mark Roe ; Jeroen den Hertog ; David Barford
- 刊名：Biochemistry
- 出版年：2007
- 出版时间：January 23, 2007
- 年：2007
- 卷：46
- 期：3
- 页码：709 - 719
- 全文大小：1279K
- 年卷期：v.46,no.3(January 23, 2007)
- ISSN：1520-4995
文摘
Protein tyrosine phosphatases (PTPs) are fundamental to the regulation of cellular signallingcascades triggered by protein tyrosine kinases. Most receptor-like PTPs (RPTPs) comprise two tandemPTP domains, with only the membrane proximal domains (D1) having significant phosphatase activity;the membrane distal domains (D2) display little to no catalytic activity. Intriguingly, however, manyRPTP D2s share the catalytically essential Cys and Arg residues of D1s. D2 of RPTP
may function asa redox sensor that mediates regulation of D1 via reactive oxygen species. Oxidation of Cys723 of RPTPD2 (equivalent to PTP catalytic Cys residues) stabilizes RPTP dimers, induces rotational coupling, andis required for inactivation of D1 phosphatase activity. Here, we investigated the structural consequencesof RPTP D2 oxidation. Exposure of RPTP D2 to oxidants promotes formation of a cyclic sulfenamidespecies, a reversibly oxidized state of Cys723, accompanied by conformational changes of the D2 catalyticsite. The cyclic sulfenamide is highly resistant to terminal oxidation to sulfinic and sulfonic acids.Conformational changes associated with RPTP D2 oxidation have implications for RPTP quaternarystructure and allosteric regulation of D1 phosphatase activity.
may function asa redox sensor that mediates regulation of D1 via reactive oxygen species. Oxidation of Cys723 of RPTPD2 (equivalent to PTP catalytic Cys residues) stabilizes RPTP dimers, induces rotational coupling, andis required for inactivation of D1 phosphatase activity. Here, we investigated the structural consequencesof RPTP D2 oxidation. Exposure of RPTP D2 to oxidants promotes formation of a cyclic sulfenamidespecies, a reversibly oxidized state of Cys723, accompanied by conformational changes of the D2 catalyticsite. The cyclic sulfenamide is highly resistant to terminal oxidation to sulfinic and sulfonic acids.Conformational changes associated with RPTP D2 oxidation have implications for RPTP quaternarystructure and allosteric regulation of D1 phosphatase activity.