Scholarlink

<p>Protein phosphorylation is a universal regulatory mechanism, controlling virtually all aspects of bacterial physiology and pathogenesis, yet histidine phosphorylation remains among the least understood. The histidine phosphocarrier protein HPr not only drives bacterial glucose transmembrane uptake through the phosphotransferase system (PTS), but also controls key enzymes for central carbon metabolism, including glycogen phosphorylase (GP). Here we report cryoEM structures of multimeric <i>Escherichia coli</i> <sup>Ec</sup>GP and their complexes with <sup>Ec</sup>HPr. The EM maps reveal an unanticipated density at H806 of <sup>Ec</sup>GP, consistent with histidine phosphorylation within a histidine-rich pocket at the N-terminal domain. Enzymatic assays reveal that <sup>Ec</sup>HPr transfers a phosphoryl group to the <i>N</i>1 position of a histidine residue in <sup>Ec</sup>GP. Through an integrative structural, mutational and functional approach, we uncover the molecular basis of <sup>Ec</sup>HPr- <sup>Ec</sup>GP selectivity and define the allosteric mechanism by which <sup>Ec</sup>HPr regulates <sup>Ec</sup>GP. We establish histidine phosphorylation as a mechanism of GP regulation, expanding the traditional paradigm of glycogen metabolism control in bacteria.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Structural basis for phosphorylation and allosteric regulation of bacterial glycogen phosphorylase by histidine phosphocarrier protein

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月27日

查看全文
  • Valerio Di Domenico,
  • Jorick Franceus,
  • Leonardo Mastrella,
  • Emma De Beul,
  • Adrià Alcaide-Jiménez,
  • Francisco Paredes-Martínez,
  • Juan Carlos Villegas-Ruiz,
  • Elena Holden,
  • Alejandro Delgado Rey,
  • Cecilia D’Angelo,
  • Javier O. Cifuente,
  • Weston B. Struwe,
  • Ricardo M. Biondi,
  • Alberto Marina,
  • Sean R. Connell,
  • Justin L. P. Benesch,
  • Patricia Casino,
  • Christophe Colleoni,
  • Tom Desmet,
  • Marcelo E. Guerin

摘要

Protein phosphorylation is a universal regulatory mechanism, controlling virtually all aspects of bacterial physiology and pathogenesis, yet histidine phosphorylation remains among the least understood. The histidine phosphocarrier protein HPr not only drives bacterial glucose transmembrane uptake through the phosphotransferase system (PTS), but also controls key enzymes for central carbon metabolism, including glycogen phosphorylase (GP). Here we report cryoEM structures of multimeric Escherichia coli EcGP and their complexes with EcHPr. The EM maps reveal an unanticipated density at H806 of EcGP, consistent with histidine phosphorylation within a histidine-rich pocket at the N-terminal domain. Enzymatic assays reveal that EcHPr transfers a phosphoryl group to the N1 position of a histidine residue in EcGP. Through an integrative structural, mutational and functional approach, we uncover the molecular basis of EcHPr- EcGP selectivity and define the allosteric mechanism by which EcHPr regulates EcGP. We establish histidine phosphorylation as a mechanism of GP regulation, expanding the traditional paradigm of glycogen metabolism control in bacteria.