Review
Biochemistry & Molecular Biology
Munishwar Nath Gupta, Vladimir N. Uversky
Summary: This article discusses the importance of protein multi-specificity, with a focus on the concept of enzyme specificity and the phenomenon of moonlighting. It provides examples of protein moonlighting and outlines the role of protein plasticity and intrinsic disorder in blurring the distinction between enzymes and other biologically active proteins. Additionally, it updates information on the significant roles of moonlighting in human diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Kevin Drew, John B. Wallingford, Edward M. Marcotte
Summary: Researchers developed a machine learning framework to identify nearly 7,000 protein complexes in human cells, resulting in the creation of the more accurate and comprehensive resource hu.MAP 2.0 and proposing many new hypotheses. The study also identified promiscuous proteins that participate in multiple complexes, suggesting potential moonlighting roles.
MOLECULAR SYSTEMS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ravi Pratap Singh, Neha Saini, Gaurav Sharma, R. Rahisuddin, Madhuri Patel, Abhishek Kaushik, S. Kumaran
Summary: The study develops an iterative sequence matching method to reveal the moonlighting biochemistry of cysteine synthase (CS) and validates the predictions through analytical and structural approaches. Experimental results show that five previously unknown CS-binding proteins involved in diverse metabolic processes interact with CS in a species-specific manner. Signature characteristics of protein-protein interactions highly match with known CS-Binder, indicating the potential for further investigation into protein-specific moonlighting properties of multifunctional proteins.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Review
Microbiology
Nicole J. Curtis, Krupa J. Patel, Amina Rizwan, Constance J. Jeffery
Summary: This mini-review discusses examples of moonlighting proteins in fungi, revealing their roles in transcription and DNA metabolism, translation and RNA metabolism, protein folding, regulation of protein function, and their interaction with other cell types and host proteins.
Article
Pharmacology & Pharmacy
Rafael Moran-Torres, David A. Castillo Gonzalez, Maria Luisa Duran-Pasten, Beatriz Aguilar-Maldonado, Susana Castro-Obregon, Gabriel Del Rio
Summary: Cell penetrating peptides (CPPs) can pass through biological membranes to deliver impermeable molecules into cells, but lack specificity in internalization. Targeting and activation approaches have been used to address this issue, resulting in multifunctional peptides with increased lengths and synthesis costs.
Article
Microbiology
Esther Prados de la Torre, Antonio Rodriguez-Franco, Manuel J. Rodriguez-Ortega
Summary: This study compared the exoproteome fraction of different human clinical isolates of Streptococcus suis, revealing key proteins with antigenic potential and providing important insights for further research into the pathogenic mechanisms of this bacterium.
Article
Cell Biology
Justyna Karkowska-Kuleta, Ewelina Wronowska, Dorota Satala, Marcin Zawrotniak, Grazyna Bras, Andrzej Kozik, Angela H. Nobbs, Maria Rapala-Kozik
Summary: The study revealed that enolase is more abundant on the surface of hyphal forms in Candida albicans compared to yeast-like cells, and Als3 is an important partner for the surface display of enolase. The N-terminal region and central repeat domain of Als3 are essential for its interaction with enolase, influencing the binding of host plasma proteins on the candidal cell surface and potentially modulating plasma proteolytic cascades to affect homeostasis and inflammation during infection.
CELLULAR MICROBIOLOGY
(2021)
Article
Biology
Maria J. Lorite, Ariana Casas-Roman, Lourdes Girard, Sergio Encarnacion, Natalia Diaz-Garrido, Josefa Badia, Laura Baldoma, Daniel Perez-Mendoza, Juan Sanjuan
Summary: The second messenger cyclic diguanylate (cdG) is known to play a crucial role in biofilm formation in bacteria. This study found that high levels of cdG not only promote the secretion of proteins involved in adhesion and biofilm formation, but also facilitate the export of cytoplasmic proteins. These cytoplasmic proteins have been previously described as moonlighting or multifunctional proteins, often found extracellularly or at the bacterial cell surface. The findings suggest that cdG promotes the active exportation of cytoplasmic proteins through yet unknown mechanisms involving post-translational modification.
Review
Biochemistry & Molecular Biology
Carolina Rodriguez-Saavedra, Luis Enrique Morgado-Martinez, Andres Burgos-Palacios, Beatriz King-Diaz, Montserrat Lopez-Coria, Sobeida Sanchez-Nieto
Summary: Moonlighting proteins, like Hexokinase, have multiple unrelated functions in different organisms, with the most common function being a glucose sensor across multiple kingdoms. These proteins play diverse roles, impacting responses to nutritional challenges and disease. Regulation mechanisms can influence their subcellular localization, oligomeric state, and interactions with other molecules, affecting their moonlighting functions.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Amanda Pritzlaff, Guillaume Ferre, Emma Mulry, Ling Lin, Niloofar Gopal Pour, Daniel A. Savin, Michael E. Harris, Matthew T. Eddy
Summary: PEGylation is a promising method to improve protein stability, but the underlying mechanism is not well understood. This study used a structural and biophysical approach to investigate the effects of PEGylation on the carbohydrate recognition domain of human galectin-3. The results revealed the potential role of charged residues in PEG localization and provided insights for the rational design of conjugates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Microbiology
Yetunde A. Ayinuola, Sheiny Tjia-Fleck, Bradley M. Readnour, Zhong Liang, Olawole Ayinuola, Lake N. Paul, Shaun W. Lee, Vincent A. Fischetti, Victoria A. Ploplis, Francis J. Castellino
Summary: The proteolytic activity of human plasmin is utilized by cells to enhance migration potential. Streptococcus pyogenes surface M-protein interacts strongly with human host plasminogen, while moonlighting proteins such as enolase also play a role in plasminogen acquisition.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Carme Nuno-Cabanes, Susana Rodriguez-Navarro
Summary: Gene expression is a complex process involving multiple steps regulated by different factors. The SAGA coactivator complex plays a crucial role in this process by mediating histone acetylation and deubiquitination. Most SAGA subunits interact physically with proteins beyond the complex, possibly representing independent functions or a way to enhance SAGA multifunctionality.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2021)
Article
Multidisciplinary Sciences
Fiona Whelan, Aleix Lafita, James Gilburt, Clement Degut, Samuel C. Griffiths, Huw T. Jenkins, Alexander N. St John, Emanuele Paci, James W. B. Moir, Michael J. Plevin, Christoph G. Baumann, Alex Bateman, Jennifer R. Potts
Summary: Changes at the cell surface enable bacteria to survive in dynamic environments, with Periscope Proteins identified as a common mechanism for bacterial surface alteration through protein length variation. These proteins, forming elongated rod-like structures, can have over 50 distinct variants implicated in host colonization and biofilm formation. While sequence divergence in large multidomain proteins may reduce misfolding between domains, Periscope Proteins break this rule and suggest that their length variability is crucial in regulating bacterial interactions with host surfaces and the immune system.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biotechnology & Applied Microbiology
Veera Kainulainen, Carina Von Schantz-Fant, Ruusu-Maria Kovanen, Swapnil Potdar, Karoliina Laamanen, Jani Saarela, Reetta Satokari
Summary: In this study, a high-throughput screening assay was developed to explore the binding receptors of intestinal epithelial cells for Bifidobacterium bifidum. Four cell surface proteins, SERPINB3, LGICZ1, PKD1, and PAQR6, were identified as potential receptors. Blocking these host cell proteins significantly decreased the binding of B. bifidum to the intestinal cell lines. These proteins are involved in the regulation of cellular processes related to proliferation, differentiation, apoptosis, inflammation, and immunity, providing insights into the mechanisms of B. bifidum-host interactions and its regulation of intestinal homeostasis.
NPJ BIOFILMS AND MICROBIOMES
(2022)
Article
Biochemical Research Methods
Yingjun Ma, Junjiang Zhong
Summary: Viral infection involves a large number of protein-protein interactions (PPIs) between the virus and the host, and the identification of these PPIs plays an important role in revealing viral infection and pathogenesis. We propose a novel computational framework, LTDSSL, to determine human-virus PPIs under different disease types. Experimental results show that LTDSSL has better predictive performance for both new disease types and new triples than the state-of-the-art methods.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Sineewanlaya Wichit, Rodolphe Hamel, Andreas Zanzoni, Fode Diop, Alexandra Cribier, Loic Talignani, Abibatou Diack, Pauline Ferraris, Florian Liegeois, Serge Urbach, Peeraya Ekchariyawat, Andres Merits, Hans Yssel, Monsef Benkirane, Dorothee Misse
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Review
Biochemistry & Molecular Biology
Andreas Zanzoni, Diogo M. Ribeiro, Christine Brun
CELLULAR AND MOLECULAR LIFE SCIENCES
(2019)
Article
Biochemistry & Molecular Biology
Diogo M. Ribeiro, Alexis Prod'homme, Adrien Teixeira, Andreas Zanzoni, Christine Brun
NUCLEIC ACIDS RESEARCH
(2020)
Article
Mathematical & Computational Biology
Sebastien A. Choteau, Audrey Wagner, Philippe Pierre, Lionel Spinelli, Christine Brun
Summary: High-throughput technologies have revealed the presence of non-canonical short open reading frames (sORFs) on most eukaryotic ribonucleic acids. MetamORF provides a repository of unique sORFs identified in the human and mouse genomes for future investigations. The database offers new analyses at locus, gene, transcript, and ORF levels and is accessible through a user-friendly web interface.
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
(2021)
Review
Microbiology
Deeya Saha, Marta Iannuccelli, Christine Brun, Andreas Zanzoni, Luana Licata
Summary: Viral infections are a major cause of human diseases, and understanding the virus-host protein-protein interactions is crucial for developing treatments. The interactions have been captured in molecular interaction databases, allowing for further bioinformatic and network studies. Network analysis of virus-host interactomes helps us understand the effects of viral infection on the host and the key proteins and pathways targeted by the virus.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Cell Biology
Bertrand Fabre, Sebastien A. Choteau, Carine Duboe, Carole Pichereaux, Audrey Montigny, Dagmara Korona, Michael J. Deery, Mylene Camus, Christine Brun, Odile Burlet-Schiltz, Steven Russell, Jean-Philippe Combier, Kathryn S. Lilley, Serge Plaza
Summary: Recent studies have found that many small proteins are overlooked during the annotation of protein-coding genes. These alternative proteins, which have short open reading frames or are monocistronic, have failed to be properly characterized. Some of these alternative proteins have been shown to have biological activity and are involved in a wide range of functions. However, the exploration of the alternative proteome is limited to a small number of species. In this article, a deep peptidomics workflow was used to identify 401 alternative proteins in the fruit fly Drosophila melanogaster. Subcellular localization, protein domains, and short linear motifs were predicted for 235 of these alternative proteins, providing insight into their specific functions. Several alternative proteins were found to have higher abundances than their canonical counterparts, suggesting that they are the main products of their corresponding genes. Additionally, 14 alternative proteins were found to have developmentally regulated expression patterns and 10 were induced upon heat-shock treatment of embryos, indicating stage or stress-specific production of alternative proteins.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Dae-Kyum Kim, Benjamin Weller, Chung-Wen Lin, Dayag Sheykhkarimli, Jennifer J. Knapp, Guillaume Dugied, Andreas Zanzoni, Carles Pons, Marie J. Tofaute, Sibusiso B. Maseko, Kerstin Spirohn, Florent Laval, Luke Lambourne, Nishka Kishore, Ashyad Rayhan, Mayra Sauer, Veronika Young, Hridi Halder, Nora Marin-de la Rosa, Oxana Pogoutse, Alexandra Strobel, Patrick Schwehn, Roujia Li, Simin T. Rothballer, Melina Altmann, Patricia Cassonnet, Atina G. Cote, Lena Elorduy Vergara, Isaiah Hazelwood, Betty B. Liu, Maria Nguyen, Ramakrishnan Pandiarajan, Bushra Dohai, Patricia A. Rodriguez Coloma, Juline Poirson, Paolo Giuliana, Luc Willems, Mikko Taipale, Yves Jacob, Tong Hao, David E. Hill, Christine Brun, Jean-Claude Twizere, Daniel Krappmann, Matthias Heinig, Claudia Falter, Patrick Aloy, Caroline Demeret, Marc Vidal, Michael A. Calderwood, Frederick P. Roth, Pascal Falter-Braun
Summary: A study mapping the contactome between SARS-CoV-2 and human host proteins uncovers an inhibitor of viral replication and connects it to COVID-19 severity and human genetic architecture, providing important insights for therapy design and drug development.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Saswati Saha, Laurent Perrin, Laurence Roder, Christine Brun, Lionel Spinelli
Summary: In this article, a novel method called epiMEIF is proposed for detecting higher-order epistatic interactions from GWAS data, improving the detection of genetic architecture underlying complex phenotypes.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Saswati Saha, Lionel Spinelli, Jaime A. Castro Mondragon, Anais Kervadec, Michaela Lynott, Laurent Kremmer, Laurence Roder, Sallouha Krifa, Magali Torres, Christine Brun, Georg Vogler, Rolf Bodmer, Alexandre R. Colas, Karen Ocorr, Laurent Perrin
Summary: Studying the cardiac performance variations in Drosophila reveals genetic networks associated with natural variation of cardiac traits and identifies genes related to cardiac function variations. The findings in fruit flies can potentially accelerate the discovery of heart diseases in humans.
Article
Multidisciplinary Sciences
Andreas Zanzoni, Lionel Spinelli, Diogo M. Ribeiro, Gian Gaetano Tartaglia, Christine Brun
SCIENTIFIC REPORTS
(2019)