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Article ; Online: Kinetic and catalytic features of N-myristoyltransferases.

Rivière, Frédéric / Monassa, Paul / Giglione, Carmela / Meinnel, Thierry

2023 Volume 684, Page(s) 167–190

Abstract: N-myristoyltransferases (NMTs) are members of the large family of GCN5-related N-acetyltransferases (GNATs). NMTs mainly catalyze eukaryotic protein myristoylation, an essential modification tagging protein N-termini and allowing successive subcellular ... ...

Abstract	N-myristoyltransferases (NMTs) are members of the large family of GCN5-related N-acetyltransferases (GNATs). NMTs mainly catalyze eukaryotic protein myristoylation, an essential modification tagging protein N-termini and allowing successive subcellular membrane targeting. NMTs use myristoyl-CoA (C14:0) as major acyl donor. NMTs were recently found to react with unexpected substrates including lysine side-chains and acetyl-CoA. This chapter details the kinetic approaches that have allowed the characterization of the unique catalytic features of NMTs in vitro.
MeSH term(s)	Amino Acid Sequence ; Acyltransferases/chemistry
Chemical Substances	glycylpeptide N-tetradecanoyltransferase (EC 2.3.1.97) ; Acyltransferases (EC 2.3.-)
Language	English
Publishing date	2023-03-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1557-7988
ISSN (online)	1557-7988
DOI	10.1016/bs.mie.2023.02.018
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Article: Phospholipases A and Lysophospholipases in protozoan parasites.

Hervé, Perrine / Monic, Sarah / Bringaud, Frédéric / Rivière, Loïc

Microbial cell (Graz, Austria)

2023 Volume 10, Issue 10, Page(s) 204–216

Abstract: Phospholipases (PLs) and Lysophospholipases (LysoPLs) are a diverse group of esterases responsible for phospholipid or lysophospholipid hydrolysis. They are involved in several biological processes, including lipid catabolism, modulation of the immune ... ...

Abstract	Phospholipases (PLs) and Lysophospholipases (LysoPLs) are a diverse group of esterases responsible for phospholipid or lysophospholipid hydrolysis. They are involved in several biological processes, including lipid catabolism, modulation of the immune response and membrane maintenance. PLs are classified depending on their site of hydrolysis as PLA1, PLA2, PLC and PLD. In many pathogenic microorganisms, from bacteria to fungi, PLAs and LysoPLs have been described as critical virulence and/or pathogenicity factors. In protozoan parasites, a group containing major human and animal pathogens, growing literature show that PLAs and LysoPLs are also involved in the host infection. Their ubiquitous presence and role in host-pathogen interactions make them particularly interesting to study. In this review, we summarize the literature on PLAs and LysoPLs in several protozoan parasites of medical relevance, and discuss the growing interest for them as potential drug and vaccine targets.
Language	English
Publishing date	2023-10-02
Publishing country	Austria
Document type	Journal Article ; Review
ZDB-ID	2814756-X
ISSN	2311-2638
ISSN	2311-2638
DOI	10.15698/mic2023.10.805
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Article ; Online: Biochemical and structural analysis of N-myristoyltransferase mediated protein tagging.

Monassa, Paul / Rivière, Frédéric / Dian, Cyril / Frottin, Frédéric / Giglione, Carmela / Meinnel, Thierry

Methods in enzymology

2023 Volume 684, Page(s) 135–166

Abstract: N-terminal myristoylation is an essential eukaryotic modification crucial for cellular homeostasis in the context of many physiological processes. Myristoylation is a lipid modification resulting in a C14 saturated fatty acid addition. This modification ... ...

Abstract	N-terminal myristoylation is an essential eukaryotic modification crucial for cellular homeostasis in the context of many physiological processes. Myristoylation is a lipid modification resulting in a C14 saturated fatty acid addition. This modification is challenging to capture due to its hydrophobicity, low abundance of target substrates, and the recent discovery of unexpected NMT reactivity including myristoylation of lysine side chains and N-acetylation in addition to classical N-terminal Gly-myristoylation. This chapter details the high-end approaches developed to characterize the different features of N-myristoylation and its targets through in vitro and in vivo labeling.
MeSH term(s)	Acyltransferases/metabolism ; Myristic Acid/metabolism ; Fatty Acids ; Lysine
Chemical Substances	glycylpeptide N-tetradecanoyltransferase (EC 2.3.1.97) ; Acyltransferases (EC 2.3.-) ; Myristic Acid (0I3V7S25AW) ; Fatty Acids ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2023-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1557-7988
ISSN (online)	1557-7988
DOI	10.1016/bs.mie.2023.02.016
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Article ; Online: MRI classification of uterosacral ligament involvement in endometriosis: the Hôtel-Dieu (HTD) classification.

Hélage, Siegfried / Rivière, Lucas / Buy, Jean-Noël / Bordonné, Corinne / Préaux, Frédéric / Just, Pierre-Alexandre / Aflak, Nizar / Rousset, Pascal / Dion, Élisabeth

The British journal of radiology

2024

Abstract: Objective: This study aimed to establish the first-ever MRI classification of uterosacral ligament (USL) involvement in deep endometriosis (DIE), based on reliable preoperative MRI features correlated with positive predictive values (PPVs) determined ... ...

Abstract	Objective: This study aimed to establish the first-ever MRI classification of uterosacral ligament (USL) involvement in deep endometriosis (DIE), based on reliable preoperative MRI features correlated with positive predictive values (PPVs) determined through histopathological analysis. Methods: 22 women underwent surgery with histopathology due to symptoms highly suggestive of endometriosis. The 22 preoperative MRIs were analyzed retrospectively, blinded to histopathology, and a classification of preoperative aspect of USLs linked to PPVs was designed. Results: According to their aspect, six radiological types of USL were identified. The "L-category" corresponded to linear types, with regular or irregular margins, including types 1, 2, 3A and 3B. The "N-category" corresponded to hemorrhagic or nodular types, including types 4, 5A, 5B and 6. For the L-category, PPVs ranged from 75% to 88%, depending on the USL radiological type. For the N-category, PPVs were 100% for each type. In women with endometriosis symptoms, MRI underestimated USL involvement, especially for type 1. Among the six uterus with lateral deviation, only one false positive result concerning the stretched USL was induced. Conclusions: In women with endometriosis symptoms, our MRI classification identified two USL categories, corresponding to two kinds of PPV; in these symptomatic patients, a normal MRI does not rule out a DIE diagnosis. Advances in knowledge: Our MRI classification of USL involvement in endometriosis may be used as a noninvasive staging of the disease, much clearer for clinicians and patients. Hence, we are able to propose a suitable diagnostic and therapeutic procedure for each radiological type.
Language	English
Publishing date	2024-04-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2982-8
ISSN	1748-880X ; 0007-1285
ISSN (online)	1748-880X
ISSN	0007-1285
DOI	10.1093/bjr/tqae072
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Article: Utility of indium-111 platelet scintigraphy for understanding the mechanism of thrombocytopenia associated with myelodysplastic syndromes and chronic myelomonocytic leukemia.

Durand, Pauline / Pottier, Valérie / Mesguich, Charles / Debordeaux, Frédéric / Lazaro, Estibaliz / Viallard, Jean-François / Rivière, Etienne

Experimental hematology & oncology

2023 Volume 12, Issue 1, Page(s) 50

Abstract: Background: Thrombocytopenia occurs in 60% of patients with myelodysplastic syndromes (MDS), increasing the risk of life-threatening haemorrhage in this population of mainly old patients with comorbidities. However, data are scare regarding immune ... ...

Abstract	Background: Thrombocytopenia occurs in 60% of patients with myelodysplastic syndromes (MDS), increasing the risk of life-threatening haemorrhage in this population of mainly old patients with comorbidities. However, data are scare regarding immune thrombocytopenia (ITP) secondary to MDS. Aim: We analyzed the utility of indium-111 platelet scintigraphy (IPS) to better characterize the mechanisms of thrombocytopenia in 21 adult patients with MDS. Methods: Adult patients with a definite diagnosis of MDS according to the international criteria who underwent IPS between 2009 and 2018 because of an increased bleeding risk were retrospectively selected. Autologous 111Indium platelet labelling was performed with a technique similar to that described previously using a standardized method. Results: Platelet lifespan ≤ 6 days identified patients with peripheral platelet destruction. Taking into account the response to ITP-directed therapies after IPS, the sensitivity, specificity, and positive and negative predictive values of IPS were 100%, 84.6%, 80%, and 100%, respectively. Conclusion: We show that IPS can be a useful tool to identify the mechanism and guide treatment of a chronic thrombocytopenia increasing the bleeding risk in patients with MDS.
Language	English
Publishing date	2023-05-30
Publishing country	England
Document type	Letter
ZDB-ID	2669066-4
ISSN	2162-3619
ISSN	2162-3619
DOI	10.1186/s40164-023-00414-1
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Article: A Continuous Assay Set to Screen and Characterize Novel Protein N-Acetyltransferases Unveils Rice General Control Non-repressible 5-Related N-Acetyltransferase2 Activity.

Asensio, Thomas / Dian, Cyril / Boyer, Jean-Baptiste / Rivière, Frédéric / Meinnel, Thierry / Giglione, Carmela

Frontiers in plant science

2022 Volume 13, Page(s) 832144

Abstract: Protein N-acetyltransferases (NATs) belong to the general control non-repressible 5 (Gcn5)-related N-acetyltransferases (GNATs) superfamily. GNATs catalyze the transfer of acetyl from acetyl-CoA to the reactive amine moiety of a wide range of acceptors. ... ...

Abstract	Protein N-acetyltransferases (NATs) belong to the general control non-repressible 5 (Gcn5)-related N-acetyltransferases (GNATs) superfamily. GNATs catalyze the transfer of acetyl from acetyl-CoA to the reactive amine moiety of a wide range of acceptors. NAT sequences are difficult to distinguish from other members of the GNAT superfamily and there are many uncharacterized GNATs. To facilitate the discovery and characterization of new GNATs, we have developed a new continuous, non-radioactive assay. This assay is virtually independent of the substrate and can be used to get substrate specificity hints. We validated first the assay with the well-characterized
Language	English
Publishing date	2022-02-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2613694-6
ISSN	1664-462X
ISSN	1664-462X
DOI	10.3389/fpls.2022.832144
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Article ; Online: Structural and Large-scale Analysis Unveil the Intertwined Paths Promoting NMT-catalyzed Lysine and Glycine Myristoylation.

Rivière, Frédéric / Dian, Cyril / Dutheil, Rémi F / Monassa, Paul / Giglione, Carmela / Meinnel, Thierry

Journal of molecular biology

2022 Volume 434, Issue 22, Page(s) 167843

Abstract: N-myristoyltransferases (NMTs) catalyze protein myristoylation, a lipid modification crucial for cell survival and a range of pathophysiological processes. Originally thought to modify only N-terminal glycine α-amino groups (G-myristoylation), NMTs were ... ...

Abstract	N-myristoyltransferases (NMTs) catalyze protein myristoylation, a lipid modification crucial for cell survival and a range of pathophysiological processes. Originally thought to modify only N-terminal glycine α-amino groups (G-myristoylation), NMTs were recently shown to also modify lysine ε-amino groups (K-myristoylation). However, the clues ruling NMT-dependent K-myristoylation and the full range of targets are currently unknown. Here we combine mass spectrometry, kinetic studies, in silico analysis, and crystallography to identify the specific features driving each modification. We show that direct interactions between the substrate's reactive amino group and the NMT catalytic base promote K-myristoylation but with poor efficiency compared to G-myristoylation, which instead uses a water-mediated interaction. We provide evidence of depletion of proteins with NMT-dependent K-myristoylation motifs in humans, suggesting evolutionary pressure to prevent this modification in favor of G-myristoylation. In turn, we reveal that K-myristoylation may only result from post-translational events. Our studies finally unravel the respective paths towards K-myristoylation or G-myristoylation, which rely on a very subtle tradeoff embracing the chemical landscape around the reactive group.
MeSH term(s)	Humans ; Acyltransferases/chemistry ; Catalysis ; Glycine/chemistry ; Kinetics ; Lysine/chemistry ; Myristic Acid/chemistry ; Protein Processing, Post-Translational
Chemical Substances	Acyltransferases (EC 2.3.-) ; Glycine (TE7660XO1C) ; Lysine (K3Z4F929H6) ; Myristic Acid (0I3V7S25AW) ; glycylpeptide N-tetradecanoyltransferase (EC 2.3.1.97)
Language	English
Publishing date	2022-09-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2022.167843
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Article ; Online: Infection with Influenzavirus A in a murine model induces epithelial bronchial lesions and distinct waves of innate immune-cell recruitment.

Rivière, Frédéric / Burger, Julien / Lefèvre, François / Garnier, Annabelle / Vigne, Clarisse / Tournier, Jean-Nicolas / Billon-Denis, Emmanuelle

Frontiers in immunology

2023 Volume 14, Page(s) 1241323

Abstract: Introduction: Inflammatory lesions after Influenza A viruses (IAV) are potential therapeutic target for which better understanding of post-infection immune mechanisms is required. Most studies to evaluate innate immune reactions induced by IAV are based ...

Abstract	Introduction: Inflammatory lesions after Influenza A viruses (IAV) are potential therapeutic target for which better understanding of post-infection immune mechanisms is required. Most studies to evaluate innate immune reactions induced by IAV are based on quantitative/functional methods and anatomical exploration is most often non-existent. We aimed to study pulmonary damage and macrophage recruitment using two-photon excitation microscopy (TPEM) after IAV infection. Methods: We infected C57BL/6 CD11c Results: TPEM provided complementary data to flow cytometry and cytokine assays by allowing observation of bronchial epithelium lesions and spreading of local infection. Addition of F4/80-BV421 staining allowed us to precisely determine timing of recruitment and pulmonary migration of macrophages. Conclusion: After IAV infection, we were able to explore structural consequences and successive waves of innate immune cell recruitment. By combining microscopy, flow cytometry and chemokine measurements, we describe novel and precise scenario of innate immune response against IAV.
MeSH term(s)	Animals ; Mice ; Humans ; Mice, Inbred C57BL ; Alphainfluenzavirus ; Disease Models, Animal ; Influenza A Virus, H1N1 Subtype ; Influenza A virus ; Immunity, Innate ; Influenza, Human ; Microscopy, Fluorescence ; Cytokines
Chemical Substances	Cytokines
Language	English
Publishing date	2023-08-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1241323
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Article ; Online: Streptococcus pyogenes Cas9 ribonucleoprotein delivery for efficient, rapid and marker-free gene editing in Trypanosoma and Leishmania.

Asencio, Corinne / Hervé, Perrine / Morand, Pauline / Oliveres, Quentin / Morel, Chloé Alexandra / Prouzet-Mauleon, Valérie / Biran, Marc / Monic, Sarah / Bonhivers, Mélanie / Robinson, Derrick Roy / Ouellette, Marc / Rivière, Loïc / Bringaud, Frédéric / Tetaud, Emmanuel

Molecular microbiology

2024

Abstract: Kinetoplastids are unicellular eukaryotic flagellated parasites found in a wide range of hosts within the animal and plant kingdoms. They are known to be responsible in humans for African sleeping sickness (Trypanosoma brucei), Chagas disease ( ... ...

Abstract	Kinetoplastids are unicellular eukaryotic flagellated parasites found in a wide range of hosts within the animal and plant kingdoms. They are known to be responsible in humans for African sleeping sickness (Trypanosoma brucei), Chagas disease (Trypanosoma cruzi), and various forms of leishmaniasis (Leishmania spp.), as well as several animal diseases with important economic impact (African trypanosomes, including Trypanosoma congolense). Understanding the biology of these parasites necessarily implies the ability to manipulate their genomes. In this study, we demonstrate that transfection of a ribonucleoprotein complex, composed of recombinant Streptococcus pyogenes Cas9 (SpCas9) and an in vitro-synthesized guide RNA, results in rapid and efficient genetic modifications of trypanosomatids, in marker-free conditions. This approach was successfully developed to inactivate, delete, and mutate candidate genes in various stages of the life cycle of T. brucei and T. congolense, and Leishmania promastigotes. The functionality of SpCas9 in these parasites now provides, to the research community working on these parasites, a rapid and efficient method of genome editing, without requiring plasmid construction and selection by antibiotics but requires only cloning and PCR screening of the clones. Importantly, this approach is adaptable to any wild-type parasite.
Language	English
Publishing date	2024-04-01
Publishing country	England
Document type	Journal Article
ZDB-ID	619315-8
ISSN	1365-2958 ; 0950-382X
ISSN (online)	1365-2958
ISSN	0950-382X
DOI	10.1111/mmi.15256
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Article ; Online: A large deletion in a non-coding regulatory region leads to NFKB1 haploinsufficiency in two adult siblings.

Fusaro, Mathieu / Coustal, Cyrille / Barnabei, Laura / Riller, Quentin / Heller, Marion / Ho Nhat, Duong / Fourrage, Cécile / Rivière, Sophie / Rieux-Laucat, Frédéric / Maria, Alexandre Thibault Jacques / Picard, Capucine

Clinical immunology (Orlando, Fla.)

2024 Volume 261, Page(s) 110165

Abstract: Mutations in NFkB pathway genes can cause inborn errors of immunity (IEI), with NFKB1 haploinsufficiency being a significant etiology for common variable immunodeficiency (CVID). Indeed, mutations in NFKB1 are found in 4 to 5% of in European and United ... ...

Abstract	Mutations in NFkB pathway genes can cause inborn errors of immunity (IEI), with NFKB1 haploinsufficiency being a significant etiology for common variable immunodeficiency (CVID). Indeed, mutations in NFKB1 are found in 4 to 5% of in European and United States CVID cohorts, respectively; CVID representing almost ¼ of IEI patients in European countries registries. This case study presents a 49-year-old patient with respiratory infections, chronic diarrhea, immune thrombocytopenia, hypogammaglobulinemia, and secondary lymphoma. Comprehensive genetic analysis, including high-throughput sequencing of 300 IEI-related genes and copy number variation analysis, identified a critical 2.6-kb deletion spanning the first untranslated exon and its upstream region. The region's importance was confirmed through genetic markers indicative of enhancers and promoters. The deletion was also found in the patient's brother, who displayed similar but milder symptoms. Functional analysis supported haploinsufficiency with reduced mRNA and protein expression in both patients. This case underscores the significance of copy number variation (CNV) analysis and targeting noncoding exons within custom gene panels, emphasizing the broader genomic approaches needed in medical genetics.
MeSH term(s)	Male ; Adult ; Humans ; Middle Aged ; Siblings ; Haploinsufficiency/genetics ; DNA Copy Number Variations ; NF-kappa B/genetics ; Common Variable Immunodeficiency/genetics ; Regulatory Sequences, Nucleic Acid ; NF-kappa B p50 Subunit/genetics
Chemical Substances	NF-kappa B ; NFKB1 protein, human ; NF-kappa B p50 Subunit
Language	English
Publishing date	2024-02-27
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2024.110165
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