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Cryptic disorder out of disorder: encounter between conditionally disordered CP12 and glyceraldehyde-3phosphate dehydrogenase

Abstract : Among intrinsically disordered proteins, conditionally disordered proteins undergo dramatic structural disorder rearrangements upon environmental changes and/or post-translational modifications that directly modulate their function. Quantifying the dynamics of these fluctuating proteins is extremely challenging but paramount to understanding the regulation of their function. The chloroplast protein CP12 is a model of such proteins, and acts as a redox switch by formation/disruption of its two disulfide bridges. It regulates the Calvin cycle by forming, in oxidized conditions, a supramolecular complex with glyceraldehyde-3phosphate dehydrogenase (GAPDH) and then phosphoribulokinase. In this complex both enzymes are inactive. The highly dynamic nature of CP12 has so far hindered structural characterization explaining its mode of action. Thanks to a synergistic combination of smallangle X-ray scattering, nuclear magnetic resonance and circular dichroism that drove the molecular modeling of structural ensembles, we deciphered the structural behavior of Chlamydomonas reinhardtii oxidized CP12 (CP12ox) alone and in the presence of GAPDH. Contrary to sequence-based structural predictions, the N-terminal region is unstable, oscillates at the ms timescale between helical and random conformations, and is connected through a disordered linker to its C-terminus, which forms a stable helical turn. Upon binding to GAPDH, CP12ox undergoes an induced unfolding of its N-terminus. This phenomenon called cryptic disorder contributes to decrease the entropy cost and explains CP12 unusual high affinity for its partners.
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Submitted on : Wednesday, November 16, 2022 - 3:37:25 PM
Last modification on : Thursday, November 17, 2022 - 3:13:30 AM

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Hélène Launay, Patrick Barré, Carine Puppo, Yizhi Zhang, Stéphanie Maneville, et al.. Cryptic disorder out of disorder: encounter between conditionally disordered CP12 and glyceraldehyde-3phosphate dehydrogenase. Journal of Molecular Biology, 2018, 430 (8), pp.1218-1234. ⟨10.1016/j.jmb.2018.02.020⟩. ⟨hal-03855995⟩

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