Mutagenesis of a Lotus japonicus GSK3β/Shaggy-like kinase reveals functionally conserved regulatory residues

Solovou, T.G.A.; Garagounis, Constantine; Kyriakis, E.; Bobas, Charalambos; Παπαδόπουλος, Γεώργιος; Skamnaki, Vassiliki T.; Papadopoulou, Kalliope Κ.; Leonidas, D.D.

doi:10.1016/j.phytochem.2021.112707

Cited by 4 publications

(19 citation statements)

References 73 publications

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“…Modeling the rest of the protein residues (1−100) using AlphaFold2 44 and the LjSK1 90−467 structure as a template, although it failed to produce a meaningful protein structure for the first 100 residues, the top five ranked solutions placed most of the residues at the opening of the channel leading to the active site. This conformation obstructs access to the active site and is in agreement with our previous proposal 9 for an additional activation mechanism proteolysis of the first 100 residues of LjSK1. Superposition of the LjSK1 90−467 structure to that of the GSK3β-AMP-PNP structure 41 reveals the structural characteristics of the LjSK1 90−467 active site (Figure 5).…”

Section: Resultssupporting

confidence: 92%

“…The purine base is in hydrogen-bonding distance from the main chain carbonyl oxygens of residues Glu214 and Val216, while the ribose can form hydrogen bonds with the main chain carbonyl oxygens of Val144 and Gln276 (Figure 3). The phosphate-binding site is also conserved in LjSK1 90−467 , and it is composed by Ser148, Phe144, Lys265, Gln267, Asp282, and includes Lys167 and Glu179 the two critical for activity residues 9 (Figures 2 and 4).…”

Section: Resultsmentioning

confidence: 99%

“…11,12 However, the phosphate-binding pocket, constituted by Arg96, Arg180, and Lys205 in human GSK3β, 10 is conserved in the primary structures of ASKs and LjSK1 while mutation of the equivalent to Arg96 residues (Arg178 in both proteins) reduces the activity of both plant kinases for phosphorylated substrates in vitro. 9,13 However, plant and animal GSK3s share common functional characteristics and mechanisms is still an open question. Structural studies of plant enzymes are still lagging far behind their counterparts in mammals, partly due to the conservative nature of many of the biochemical pathways between plants and animals.…”

Section: Introductionmentioning

confidence: 99%

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Biochemical and Structural Studies of LjSK1, a Lotus japonicus GSK3β/SHAGGY-like Kinase, Reveal Its Functional Role

Solovou,

Stravodimos,

Papadopoulos

et al. 2024

J. Agric. Food Chem.

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The crystal structure of a truncated form of the Lotus japonicus glycogen synthase kinase 3β (GSK3β) like kinase (LjSK1 90−467 ) has been resolved at 2.9 Å resolution, providing, for the first time, structural data for a plant GKS3β like kinase. The 3D structure of LjSK1 90−467 revealed conservation at the structural level for this plant member of the GSK3β family. However, comparative structural analysis to the human homologue revealed significant differences at the N-and C-termini, supporting the notion for an additional regulatory mechanism in plant GSK3-like kinases. Structural similarities at the catalytic site and the ATP binding site explained the similarity in the function of the human and plant protein. LjSK1 and lupeol are strongly linked to symbiotic bacterial infection and nodulation initiation. An inhibitory capacity of lupeol (IC 50 = 0.77 μM) for LjSK1 was discovered, providing a biochemical explanation for the involvement of these two molecules in nodule formation, and constituted LjSK1 as a molecular target for the discovery of small molecule modulators for crop protection and development. Studies on the inhibitory capacity of two phytogenic triterpenoids (betulinic acid and hederacoside C) to LjSK1 provided their structure−activity relationship and showed that hederacoside C can be the starting point for such endeavors.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biochemical and Structural Studies of LjSK1, a Lotus japonicus GSK3β/SHAGGY-like Kinase, Reveal Its Functional Role

Solovou,

Stravodimos,

Papadopoulos

et al. 2024

J. Agric. Food Chem.

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“…In Lotus japonicu, nodulation is mainly formed through the symbiotic nitrogen-fixing bacterium Mesorhizobium loti infection. Studies show that lotus SHAGGY-like kinase 1 (LSK1) is required to suppress nodulation (Garagounis et al, 2019;Solovou et al, 2021). Ralstonia solanacearum is a devastating soil-borne bacterium that causes wilting disease in over 200 economicallyimportant plant species.…”

Section: Gsk3s In Biotic Stressesmentioning

confidence: 99%

Regulatory network of GSK3-like kinases and their role in plant stress response

Song

Wang

et al. 2023

Front. Plant Sci.

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Glycogen synthase kinase 3 (GSK3) family members are evolutionally conserved Ser/Thr protein kinases in mammals and plants. In plants, the GSK3s function as signaling hubs to integrate the perception and transduction of diverse signals required for plant development. Despite their role in the regulation of plant growth and development, emerging research has shed light on their multilayer function in plant stress responses. Here we review recent advances in the regulatory network of GSK3s and the involvement of GSK3s in plant adaptation to various abiotic and biotic stresses. We also discuss the molecular mechanisms underlying how plants cope with environmental stresses through GSK3s-hormones crosstalk, a pivotal biochemical pathway in plant stress responses. We believe that our overview of the versatile physiological functions of GSK3s and underlined molecular mechanism of GSK3s in plant stress response will not only opens further research on this important topic but also provide opportunities for developing stress-resilient crops through the use of genetic engineering technology.

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“…Previous study indicated that this kinase is involved in nodule development. Interestingly, removal of a 98 residue-long N-terminal fragment of this protein resulted in almost two-fold increase in its catalytic efficiency (Solovou et al, 2021). Classification, nomenclature and phylogenetic relationship between various representatives of this protein family are presented in Figure 1 and in Supplementary Table 1.…”

Section: Introductionmentioning

confidence: 99%

Glycogen synthase kinases in model and crop plants – From negative regulators of brassinosteroid signaling to multifaceted hubs of various signaling pathways and modulators of plant reproduction and yield

Zolkiewicz

Gruszka

2022

Front. Plant Sci.

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Glycogen synthase kinases, also known as SHAGGY-like Kinases (GSKs/SKs), are highly conserved serine/threonine protein kinases present both in animals and plants. Plant genomes contain multiple homologs of the GSK3 genes which participate in various biological processes. Plant GSKs/SKs, and their best known representative in Arabidopsis thaliana – Brassinosteroid Insentisive2 (BIN2/SK21) in particular, were first identified as components of the brassinosteroid (BR) signaling pathway. As phytohormones, BRs regulate a wide range of physiological processes in plants – from germination, cell division, elongation and differentiation to leaf senescence, and response to environmental stresses. The GSKs/SKs proteins belong to a group of several highly conserved components of the BR signaling which evolved early during evolution of this molecular relay. However, recent reports indicated that the GSKs/SKs proteins are also implicated in signaling pathways of other phytohormones and stress-response processes. As a consequence, the GSKs/SKs proteins became hubs of various signaling pathways and modulators of plant development and reproduction. Thus, it is very important to understand molecular mechanisms regulating activity of the GSKs/SKs proteins, but also to get insights into role of the GSKs/SKs proteins in modulation of stability and activity of various substrate proteins which participate in the numerous signaling pathways. Although elucidation of these aspects is still in progress, this review presents a comprehensive and detailed description of these processes and their implications for regulation of development, stress response, and reproduction of model and crop species. The GSKs/SKs proteins and their activity are modulated through phosphorylation and de-phosphorylation reactions which are regulated by various proteins. Importantly, both phosphorylations and de-phosphorylations may have positive and negative effects on the activity of the GSKs/SKs proteins. Additionally, the activity of the GSKs/SKs proteins is positively regulated by reactive oxygen species, whereas it is negatively regulated through ubiquitylation, deacetylation, and nitric oxide-mediated nitrosylation. On the other hand, the GSKs/SKs proteins interact with proteins representing various signaling pathways, and on the basis of the complicated network of interactions the GSKs/SKs proteins differentially regulate various physiological, developmental, stress response, and yield-related processes.

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Mutagenesis of a Lotus japonicus GSK3β/Shaggy-like kinase reveals functionally conserved regulatory residues

Cited by 4 publications

References 73 publications

Biochemical and Structural Studies of LjSK1, a Lotus japonicus GSK3β/SHAGGY-like Kinase, Reveal Its Functional Role

Biochemical and Structural Studies of LjSK1, a Lotus japonicus GSK3β/SHAGGY-like Kinase, Reveal Its Functional Role

Regulatory network of GSK3-like kinases and their role in plant stress response

Glycogen synthase kinases in model and crop plants – From negative regulators of brassinosteroid signaling to multifaceted hubs of various signaling pathways and modulators of plant reproduction and yield

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