Time-resolved cryo-EM reveals conformational trajectory of allosteric activation in isocitrate lyase

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bioRxiv. 2026 Apr 09;. doi: 10.64898/2026.04.08.716820

Time-resolved cryo-EM reveals conformational trajectory of allosteric activation in isocitrate lyase Cryo-Electron Microscopy

Taka J, Jung J, Guo S, Jiao W, Kwai BX, de Carvalho LP, McNeil M, Huang EY, Yu Z, Leung IK, Bashiri G

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Abstract

Isocitrate lyase 2 (ICL2) from Mycobacterium tuberculosis undergoes dramatic conformational rearrangements upon binding to the allosteric effector acetyl-CoA. Time-resolved cryo-EM captured conformational states along the ICL2 activation trajectory, revealing how acetyl-CoA binding at the allosteric sites leads to asymmetric, half-of-site activity at the catalytic centres. These findings support a conformational selection model of allostery, whereby acetyl-CoA binding shifts the pre-existing equilibrium towards an active state of the enzyme.

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Preprint: https://doi.org/10.64898/2026.04.08.716820

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Time-resolved cryo-EM reveals conformational trajectory of allosteric activation in isocitrate lyase

Abstract

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