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Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites.

التفاصيل البيبلوغرافية
العنوان: Activation loop phosphorylation and cGMP saturation of PKG regulate egress of malaria parasites.
المؤلفون: Konstantinos Koussis, Silvia Haase, Chrislaine Withers-Martinez, Helen R Flynn, Simone Kunzelmann, Evangelos Christodoulou, Fairouz Ibrahim, Mark Skehel, David A Baker, Michael J Blackman
المصدر: PLoS Pathogens, Vol 20, Iss 6, p e1012360 (2024)
بيانات النشر: Public Library of Science (PLoS), 2024.
سنة النشر: 2024
المجموعة: LCC:Immunologic diseases. Allergy
LCC:Biology (General)
مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
الوصف: The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation, including the importance of phosphorylation, remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals crucial for malaria parasite development.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1553-7366
1553-7374
Relation: https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374
DOI: 10.1371/journal.ppat.1012360
URL الوصول: https://doaj.org/article/b62bcb1860a84ec8b769e6b711c15964
رقم الأكسشن: edsdoj.b62bcb1860a84ec8b769e6b711c15964
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:15537366
15537374
DOI:10.1371/journal.ppat.1012360