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February 2, 2026Proceedings of the National Academy of SciencesOpen Access

Structural basis for pseudokinase-mediated regulation of GCN2 in the integrated stress response

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Authors

YLYixin LiuJMJagannath MisraDBD. Ryan Bhowmik

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Overview

Crystal structure analysis reveals how pseudokinase dimerization regulates GCN2 activity in stress response, indicating evolutionary conservation.

Key Points

  • The study aims to elucidate the structural role of the pseudokinase domain in regulating GCN2 during the integrated stress response.
  • Crystal structure determination of human GCN2 pseudokinase domain
  • Analysis of dimer formation and stability
  • Mutational analysis to assess impact on downstream ATF4 expression
  • AI-guided structural predictions for evolutionary conservation
  • The crystal structure reveals unique features of the human GCN2 pseudokinase domain
  • Dimerization through hydrophobic and electrostatic interactions is essential for function
  • Mutations disrupting dimerization lead to reduced ATF4 expression, affecting stress adaptation
  • The dimeric architecture is conserved across evolutionary lines.

Cite This Study

Liu et al. (2026) studied this question.

synapsesocial.com/papers/6980fecbc1c9540dea811290https://doi.org/10.1073/pnas.2526598123
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