دورية أكاديمية
أعرض في EDS

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: Koussis K; Malaria Biochemistry Laboratory, Francis Crick Institute, London, United Kingdom., Haase S; Host-Pathogen Interactions in Cryptosporidiosis Laboratory, The Francis Crick Institute, London, United Kingdom., Withers-Martinez C; Malaria Biochemistry Laboratory, Francis Crick Institute, London, United Kingdom., Flynn HR; Proteomics Science Technology Platform, The Francis Crick Institute, London, United Kingdom., Kunzelmann S; Structural Biology Science Technology Platform, The Francis Crick Institute, London, United Kingdom., Christodoulou E; Structural Biology Science Technology Platform, The Francis Crick Institute, London, United Kingdom., Ibrahim F; Proteomics Science Technology Platform, The Francis Crick Institute, London, United Kingdom., Skehel M; Proteomics Science Technology Platform, The Francis Crick Institute, London, United Kingdom., Baker DA; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom., Blackman MJ; Malaria Biochemistry Laboratory, Francis Crick Institute, London, United Kingdom.; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
المصدر: PLoS pathogens [PLoS Pathog] 2024 Jun 27; Vol. 20 (6), pp. e1012360. Date of Electronic Publication: 2024 Jun 27 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: Cyclic GMP-Dependent Protein Kinases*/metabolism , Cyclic GMP-Dependent Protein Kinases*/genetics , Cyclic GMP*/metabolism, Phosphorylation ; Malaria/parasitology ; Malaria/metabolism ; Protozoan Proteins/metabolism ; Protozoan Proteins/genetics ; Animals ; Plasmodium falciparum/metabolism ; Plasmodium falciparum/genetics ; Humans ; Signal Transduction ; Erythrocytes/parasitology ; Erythrocytes/metabolism
مستخلص: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Koussis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; CC2129 United Kingdom ARC_ Arthritis Research UK
المشرفين على المادة: EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
H2D2X058MU (Cyclic GMP)
0 (Protozoan Proteins)
تواريخ الأحداث: Date Created: 20240627 Date Completed: 20240710 Latest Revision: 20240712
رمز التحديث: 20240712
مُعرف محوري في PubMed: PMC11236177
DOI: 10.1371/journal.ppat.1012360
PMID: 38935780
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1012360