Academic Journal

One Scaffold, Two Conformations: The Ring-Flip of the Messenger InsP8 Occurs under Cytosolic Conditions

التفاصيل البيبلوغرافية
العنوان: One Scaffold, Two Conformations: The Ring-Flip of the Messenger InsP8 Occurs under Cytosolic Conditions
المؤلفون: Leonie Kurz, Peter Schmieder, Nicolás Veiga, Dorothea Fiedler
المصدر: Biomolecules; Volume 13; Issue 4; Pages: 645
بيانات النشر: Multidisciplinary Digital Publishing Institute
سنة النشر: 2023
المجموعة: MDPI Open Access Publishing
مصطلحات موضوعية: InsP 8, inositol pyrophosphates, conformation, NMR, ring-flip, molecular switch, pH sensing, metal coordination
جغرافية الموضوع: agris
الوصف: Inositol poly- and pyrophosphates (InsPs and PP-InsPs) are central eukaryotic messengers. These very highly phosphorylated molecules can exist in two distinct conformations, a canonical one with five phosphoryl groups in equatorial positions, and a “flipped” conformation with five axial substituents. Using 13C-labeled InsPs/PP-InsPs, the behavior of these molecules was investigated by 2D-NMR under solution conditions reminiscent of a cytosolic environment. Remarkably, the most highly phosphorylated messenger 1,5(PP)2-InsP4 (also termed InsP8) readily adopts both conformations at physiological conditions. Environmental factors—such as pH, metal cation composition, and temperature—strongly influence the conformational equilibrium. Thermodynamic data revealed that the transition of InsP8 from the equatorial to the axial conformation is, in fact, an exothermic process. The speciation of InsPs and PP-InsPs also affects their interaction with protein binding partners; addition of Mg2+ decreased the binding constant Kd of InsP8 to an SPX protein domain. The results illustrate that PP-InsP speciation reacts very sensitively to solution conditions, suggesting it might act as an environment-responsive molecular switch.
نوع الوثيقة: text
وصف الملف: application/pdf
اللغة: English
Relation: Biomacromolecules: Carbohydrates; https://dx.doi.org/10.3390/biom13040645
DOI: 10.3390/biom13040645
الاتاحة: https://doi.org/10.3390/biom13040645
Rights: https://creativecommons.org/licenses/by/4.0/
رقم الانضمام: edsbas.4EDF6000
قاعدة البيانات: BASE