Article
Cell Biology
Veronica Murcia-Belmonte, Maria Tercero-Diaz, Diego Barrasa-Martin, Sandra Lopez de la Vieja, Marina Munoz-Lopez, Pedro F. Esteban
Summary: The X-linked form of Kallmann syndrome is caused by mutations in the ANOS1 gene, resulting in hypogonadotropic hypogonadism and anosmia. This study reveals that anosmin 1 can enhance the activation of the PK2/PKR2 pathway and modulate its biological effects. The N-terminal region of anosmin 1 interacts with PKR2, and the whey acidic protein domain is necessary for this modulatory activity, while the cysteine-rich and FnIII.1 domains may assist in binding to PKR2 and regulating receptor activation by PK2.
CELLULAR SIGNALLING
(2022)
Article
Biochemistry & Molecular Biology
Maria Rosaria Fullone, Daniela Maftei, Martina Vincenzi, Roberta Lattanzi, Rossella Miele
Summary: Melanocortin Receptor Accessory Protein 2 (MRAP2) regulates the trafficking and signal transduction of G-protein-coupled receptors (GPCRs) involved in energy homeostasis, and its interaction with PKR2 plays a crucial role in modulating receptor localization and signaling. The prokineticin transduction system also regulates MRAP2 expression, highlighting its importance in the control of food intake.
Article
Cell Biology
Ida Casella, Caterina Ambrosio
Summary: Prokineticin receptors PKR1 and PKR2 can effectively interact with Gq/11 and Gi/o G-proteins, but less efficiently with Gs or other pertussis toxin-insensitive G proteins. They also have a strong preference for binding with β-arrestin 2 over β-arrestin 1. Additionally, prokineticin 2 is more potent than prokineticin 1 in promoting receptor binding to transduction proteins.
CELLULAR SIGNALLING
(2021)
Review
Biochemistry & Molecular Biology
Roberta Lattanzi, Rossella Miele
Summary: Prokineticins are a new class of peptides that play a crucial role in neuroinflammatory processes, regulating neuronal-glial interactions and T cell function. PK2 and PKRs are upregulated during inflammation, influencing inflammatory responses and directing T cells towards a pro-inflammatory phenotype.
Article
Biochemistry & Molecular Biology
Maria Rosaria Fullone, Roberta Lattanzi, Daniela Maftei, Maria Carmela Bonaccorsi, Rossella Miele
Summary: Prokineticin 2 (PK2) and Prokineticin 2 beta (PK2 beta) are chemokine-like proteins, with PK2 binding to both PKR1 and PKR2 receptors while PK2 beta specifically binds to PKR1. Aromatic residue clusters were found in the ECL2 of PKR2, including tryptophan 212 and Phenylalanine 198, which are crucial for ligand binding. Mutation studies showed that substituting Phenylalanine 198 with valine in PKR2 increased its specificity for the ligand PK2 beta, which normally binds to PKR1.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Review
Biochemistry & Molecular Biology
Irene Lee-Rivera, Edith Lopez, Ana Maria Lopez-Colome
Summary: This review discusses the interactions of protease activated receptors (PARs) with their own family members as well as with other types of receptors. The authors point out that the cross-talk between receptors and signaling pathways is a novel mechanism providing diversity to receptor function and playing important roles in physiology and disease.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Ran Ke, Samson Ian Sam Lok, Kailash Singh, Billy Kwok Chong Chow, Harald Janovjak, Leo Tsz On Lee
Summary: The study reveals that the formation of heterocomplexes between Kiss1R and GPER significantly reduces Kiss1R-mediated signaling, showcasing a regulatory mechanism of hypothalamic hormone receptors through receptor cooperation and modulation of receptor sensitivity in the reproductive system.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Neurosciences
Somdatta Saha, Javier Gonzalez-Maeso
Summary: Schizophrenia is a severe brain disorder that often leads to lifelong disability. First and second-generation antipsychotic medications are currently the standard treatment for schizophrenia. While antipsychotics can effectively alleviate positive symptoms in some patients, they are ineffective in treating cognitive deficits and may even cause small improvements or deterioration. This highlights the need for innovative and more efficient therapeutic targets for schizophrenia treatment.
Article
Multidisciplinary Sciences
Zhongyuan Bao, Yinlong Liu, Binglin Chen, Zong Miao, Yiming Tu, Chong Li, Honglu Chao, Yangfan Ye, Xiupeng Xu, Guangchi Sun, Pengzhan Zhao, Ning Liu, Yan Liu, Xiaoming Wang, Sin Man Lam, Valerian E. Kagan, Hulya Bayir, Jing Ji
Summary: Prokineticin-2 (Prok2) prevents neuronal cell ferroptosis after traumatic brain injury by regulating lipid peroxidation, and its administration before cortical injury reduces neuronal degeneration and improves motor and cognitive functions. This neuroprotective effect may be mediated through mechanisms involving Fbxo10.
NATURE COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Roberta Lattanzi, Cinzia Severini, Daniela Maftei, Luciano Saso, Aldo Badiani
Summary: The Prokineticin family, specifically Prokineticin 1 and Bv8/Prokineticin 2 (PROK2), interact with G protein-coupled receptors to regulate various biological functions in the central nervous system. Pathological insults can increase PROK2 expression levels and potentially contribute to neurodegenerative diseases. Despite documented physiological effects, the role of PROK2 and its receptors in neuropathological conditions remains unclear.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biology
Fanny Momboisse, Giacomo Nardi, Philippe Colin, Melanie Hery, Nelia Cordeiro, Simon Blachier, Olivier Schwartz, Fernando Arenzana-Seisdedos, Nathalie Sauvonnet, Jean-Christophe Olivio-Marin, Bernard Lagane, Thibault Lagache, Anne Brelot
Summary: This study investigated the impact of different states on the biological function and therapeutic targeting of CC chemokine receptor 5 (CCR5). The researchers used microscopy and statistical methods to track and classify the motion of different receptor subpopulations. The results showed that CCR5 exists in various ligand-free forms, stabilized by different ligands. Agonist stimulation restricted the mobility of CCR5 and led to its clustering, while inverse agonist stimulation had the opposite effect. The study also demonstrated the importance of CCR5 dimerization in its coupling to G proteins, immobilization and clustering upon activation, and receptor endocytosis.
Article
Endocrinology & Metabolism
Elizabeth K. M. Johnstone, Mohammed Akli Ayoub, Rebecca J. Hertzman, Heng B. See, Rekhati S. Abhayawardana, Ruth M. Seeber, Kevin D. G. Pfleger
Summary: This study investigated the heteromerization of AT(2) and B-2 receptors in HEK293FT cells. The results demonstrated the functional interaction between these receptors and the differences in signaling, providing important evidence for studying GPCR pharmacology and signaling diversity.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Oncology
Roberta Lattanzi, Cinzia Severini, Rossella Miele
Summary: Inflammation plays a crucial role in tumor progression. Prokineticin 2 is involved in tumor growth, angiogenesis, and metastasis. In addition to its function as an angiogenic factor and a mediator of immune cell migration, prokineticin 2 also suppresses tumor cell apoptosis, promotes their proliferation and movements necessary for metastasis. It is also associated with tumor pain and resistance responses, and may serve as a potential prognostic tumor biomarker.
Review
Biochemistry & Molecular Biology
Carla Petrella, Matteo Spaziani, Valerio D'Orazi, Luigi Tarani, Sergio Terracina, Francesca Tarani, Ginevra Micangeli, Christian Barbato, Antonio Minni, Antonio Greco, Andrea M. Isidori, Giampiero Ferraguti, Marco Fiore
Summary: Male infertility accounts for about 50% of infertility in couples, with the diagnosis and treatment process being crucial in understanding the biological origins of infertility and potential therapeutic interventions. The prokineticin system, particularly PROK2, plays a significant role in male infertility by offering new insights into testicular pathophysiology and potential therapeutic hypotheses.
Article
Biology
Roberta Lattanzi, Rossella Miele
Summary: This review summarizes the major cellular and biochemical mechanisms of prokineticins pathway regulation and discusses the potential for therapeutic intervention.
Review
Biochemistry & Molecular Biology
Antimo Cutone, Luigi Rosa, Giusi Ianiro, Maria Stefania Lepanto, Maria Carmela Bonaccorsi di Patti, Piera Valenti, Giovanni Musci
Article
Biochemistry & Molecular Biology
Roberta Lattanzi, Daniela Maftei, Maria Rosaria Fullone, Rossella Miele
Summary: Tc85, a member of trans-sialidase family, plays a crucial role in Trypanosoma cruzi parasite adhesion to mammalian cells by interacting with prokineticin receptor 2. LamG, a Tc85 domain, activates prokineticin receptor 2 and contributes to nervous system infection. The study also sheds light on the implications of the L173R mutation in Kallmann syndrome and its potential impact on parasite infection.
CELL BIOCHEMISTRY AND FUNCTION
(2021)
Article
Biophysics
Adriana E. Miele, Laura Cervoni, Aline Le Roy, Antimo Cutone, Giovanni Musci, Christine Ebel, Maria Carmela Bonaccorsi di Patti
Summary: Fep1 is an iron-responsive GATA-type transcriptional repressor with a natively unstructured nature, able to form compact complexes with DNA. Complex formation with DNA is independent of the presence of a stoichiometric [2Fe-2S] cluster, suggesting a role in recruiting other protein(s) for transcription regulation in response to changes in intracellular iron levels.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Maria Rosaria Fullone, Roberta Lattanzi, Daniela Maftei, Maria Carmela Bonaccorsi, Rossella Miele
Summary: Prokineticin 2 (PK2) and Prokineticin 2 beta (PK2 beta) are chemokine-like proteins, with PK2 binding to both PKR1 and PKR2 receptors while PK2 beta specifically binds to PKR1. Aromatic residue clusters were found in the ECL2 of PKR2, including tryptophan 212 and Phenylalanine 198, which are crucial for ligand binding. Mutation studies showed that substituting Phenylalanine 198 with valine in PKR2 increased its specificity for the ligand PK2 beta, which normally binds to PKR1.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Biochemistry & Molecular Biology
Maria Carmela Bonaccorsi di Patti, Antimo Cutone, Zuzana Pakanova, Marek Nemcovic, Peter Barath, Giovanni Musci
Summary: Ceruloplasmin is crucial for iron metabolism in vertebrates, and the production of high-quality recombinant human ceruloplasmin represents a significant advancement. Further improvement in productivity and glycoengineering is necessary for potential therapeutic use in aceruloplasminemia patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Martina Pasqua, Maria Carmela Bonaccorsi di Patti, Giulia Fanelli, Ryutaro Utsumi, Yoko Eguchi, Rita Trirocco, Gianni Prosseda, Milena Grossi, Bianca Colonna
Summary: Bacterial pathogens are able to adapt to diverse environments through cell-to-cell communication strategies and efflux pumps. Efflux pumps play a crucial role in antibiotic resistance and bacterial cell physiology, contributing to virulence potential. Major Facilitator Superfamily (MFS) multidrug efflux pumps are important in colonization, virulence, and biofilm formation in life-threatening bacterial pathogens.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Maria Carmela Bonaccorsi di Patti, Elisa Angiulli, Arianna Casini, Rosa Vaccaro, Carla Cioni, Mattia Toni
Summary: The alpha-, beta- and gamma-synucleins are small soluble proteins expressed in the nervous system of mammals and show evolutionary conservation in vertebrates. These proteins, despite sharing high homology in their N-terminal sequence, differ in molecular characteristics, expression levels and tissue distribution. The study of synucleinopathies, particularly the involvement of alpha-synuclein, provides valuable insights into the functions and evolution of synucleins in vertebrates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Giusi Ianiro, Luigi Rosa, Maria Carmela Bonaccorsi di Patti, Piera Valenti, Giovanni Musci, Antimo Cutone
Summary: Iron is an essential transition metal with crucial biological functions, but it also poses challenges for organisms due to its insolubility and formation of toxic radicals. Organisms have evolved extracellular carrier proteins to acquire and transport iron. Dysregulation of iron-proteins has been implicated in various pathological conditions, yet no resolutive therapy has been found. This review highlights the efficacy of Lactoferrin, a member of the transferrin family, in managing iron disorders associated with different pathologies.
Article
Biochemistry & Molecular Biology
Chiara Longo, Andrea Lepri, Andrea Paciolla, Antonella Messore, Daniela De Vita, Maria Carmela Bonaccorsi di Patti, Matteo Amadei, Valentina Noemi Madia, Davide Ialongo, Roberto Di Santo, Roberta Costi, Paola Vittorioso
Summary: Histone acetyltransferases (HATs) are involved in gene expression control in eukaryotes. This study focuses on a subfamily of HATs called CREB-binding proteins (CBP)/p300, which have been shown to acetylate histones and non-histone proteins. The researchers used a phenotypic assay based on Arabidopsis seedling length to evaluate the effects of a compound described as a human p300/CBP inhibitor. They also tested cinnamoyl derivatives and newly synthesized analogues. The most effective compounds were identified and their efficacy was demonstrated at a molecular level. The study confirms the usefulness of this strategy for plant epigenetic research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Pharmacology & Pharmacy
Luigi Rosa, Maria Carmela Bonaccorsi di Patti, Vadim Vasilyev, Antimo Cutone
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Antimo Cutone, Luigi Rosa, Maria Carmela Bonaccorsi di Patti, Federico Iacovelli, Maria Pia Conte, Giusi Ianiro, Alice Romeo, Elena Campione, Luca Bianchi, Piera Valenti, Mattia Falconi, Giovanni Musci
Summary: Research has found that bovine and human lactoferrins have antiviral activity against SARS-CoV-2 and can restore iron and inflammatory balance by binding to the viral glycoprotein Spike. This discovery suggests the potential use of lactoferrin as an adjunct therapy for COVID-19.
Article
Multidisciplinary Sciences
Marco Zaccaria, William Dawson, Darius Russel Kish, Massimo Reverberi, Maria Carmela Bonaccorsi di Patti, Marek Domin, Viviana Cristiglio, Bun Chan, Luca Dellafiora, Frank Gabel, Takahito Nakajima, Luigi Genovese, Babak Momeni
Summary: We investigated the detoxification of aflatoxins, fungal carcinogenic food contaminants, by laccase. Experimental comparison of two similar aflatoxins (AFB(1) and AFG(2)) showed significant differences in laccase-mediated detoxification. A multi-scale modeling approach identified substrate-specific changes needed to improve laccase's detoxification capability, and a density functional theory-based model determined the amino acid residues affecting laccase's affinity for aflatoxins. The study concluded that AFB(1) is more challenging to degrade, while AFG(2) is easier due to its lack of side products and favorable binding dynamics, highlighting opportunities to optimize laccase for aflatoxin degradation.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Giusi Ianiro, Veronica D'Ezio, Ludovica Carpinelli, Cecilia Casella, Maria Carmela Bonaccorsi di Patti, Luigi Rosa, Piera Valenti, Marco Colasanti, Giovanni Musci, Antimo Cutone, Tiziana Persichini
Summary: The study examines the effect of bovine lactoferrin (bLf) on oxidative stress and neurotoxicity in human astroglial cells infected with Human Immunodeficiency Virus (HIV-1). The results show that both forms of bLf, nat-bLf and holo-bLf, enhance the host antioxidant response and reduce reactive oxygen species-mediated damage in astrocytes. The study also demonstrates that bLf restores the physiological internalization of transferrin receptor 1 and exacerbates Tat-induced excitotoxicity on human neuronal cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Matteo Amadei, Antonella Niro, Maria Rosaria Fullone, Rossella Miele, Fabio Polticelli, Giovanni Musci, Maria Carmela Bonaccorsi di Patti
Summary: Ferroportin (Fpn), a member of the major facilitator superfamily (MFS) of transporters, is the only known iron exporter found in mammals and plays a crucial role in regulating cellular and systemic iron levels. In this study, a fluorescent amino acid (DA) was introduced into specific positions of human Fpn to investigate conformational changes during metal translocation. The results indicate metal-induced conformational transitions, providing insights into the alternating access mechanism of Fpn and advancing our understanding of iron transport.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Andrea Pasquadibisceglie, Maria Carmela Bonaccorsi di Patti, Giovanni Musci, Fabio Polticelli
Summary: This passage mainly describes the importance of iron in biology and the regulation of intracellular and extracellular iron levels through transport systems.