Article
Biochemistry & Molecular Biology
Kamila Dilimulati, Yulin Zhang, Fabiana Lica Imai, Naoto Yonezawa
Summary: Mammalian fertilization involves selective interactions between sperm proteins and oocyte zona pellucida glycoproteins. The middle region of bovine zona pellucida glycoprotein 4 (bZP4) contains a species-selective sperm-binding site. Mutations of the N-glycosylation sites in the hinge region of bZP4 and bZP3 reduce the sperm-binding activity of the complex.
Article
Cell Biology
Mirjam I. Binner, Anna Kogan, Karin Panser, Alexander Schleiffer, Victoria E. Deneke, Andrea Pauli
Summary: Fertilization is a crucial process in sexual reproduction, but the molecular mechanisms behind it are still unclear. A study on zebrafish reveals that Spaca6, a conserved protein, is essential for sperm-egg binding and fusion. The research also uncovers a previously unknown dependence of Dcst2 expression on Spaca6 in sperm.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Soledad N. Gonzalez, Valeria Sulzyk, Mariana Weigel Munoz, Patricia S. Cuasnicu
Summary: Studies on the CRISP protein family in mammalian fertilization have provided insights into their essential roles in gamete interaction and male fertility. Knockout experiments with different CRISP genes revealed their involvement in both gamete interaction and subsequent processes such as sperm transport and early embryo development within the female reproductive tract.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Ludmila Curci, Guillermo Carvajal, Valeria Sulzyk, Soledad Natalia Gonzalez, Patricia S. Cuasnicu
Summary: Inactivation of the sperm CatSper channel affects sperm fertilizing ability and function, but does not impact in vitro fertilization. Exposure to HC prior to fertilization significantly reduces in vivo fertilization, indicating the potential for developing a non-hormonal contraceptive by blocking CatSper activity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Shaogeng Tang, Yonggang Luc, Will M. Skinnere, Mrinmoy Sanyala, Polina V. Lishko, Masahito Ikawa, Peter S. Kim
Summary: A study finds that knockout of Tmem95 gene causes male sterility in mice. Using a model experiment, it is discovered that human TMEM95 can bind to hamster egg membranes, and a potential receptor-binding surface region is revealed. Further experiments show that the specific, receptor-mediated interaction between sperm TMEM95 and eggs plays a crucial role in membrane fusion during fertilization.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Yoshitaka Fujihara, Sarah Herberg, Andreas Blaha, Karin Panser, Kiyonori Kobayashi, Tamara Larasati, Maria Novatchkova, Hans-Christian Theussl, Olga Olszanska, Masahito Ikawa, Andrea Pauli
Summary: Fertilization is a crucial process initiating new individual development in sexually reproducing species. SPACA4, a sperm protein, is essential for efficient fertilization in mammals like mice, particularly for interactions with the zona pellucida. Its absence leads to subfertility in male knockout mice, with fertilization rescue observed when the zona pellucida is removed during in vitro experiments.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Ingrid Fliniaux, Guillaume Marchand, Caroline Molinaro, Mathieu Decloquement, Alain Martoriati, Matthieu Marin, Jean-Francois Bodart, Anne Harduin-Lepers, Katia Cailliau
Summary: Sialic acids are a group of monosaccharides with unique physicochemical properties that modulate the biological functions of molecules they are associated with. They play a role in various stages of the reproductive process, particularly in the formation and binding of gametes. Sialoglycoproteins form a specific coat on the surface of gametes, and marine species oocytes have specific polysialylated chains. Spermatozoa undergo crucial changes in sialic acid in the female reproductive tract, facilitating migration, survival, and binding with the oocyte.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yonggang Lu, Kentaro Shimada, Shaogeng Tang, Jingjing Zhang, Yo Ogawa, Taichi Noda, Hiroki Shibuya, Masahito Ikawa
Summary: The knockout of 1700029I15Rik impairs the biosynthesis of acrosomal membrane proteins and leads to subfertility in male mice. 1700029I15Rik interacts with proteins involved in protein processing, glycosylation, and protein trafficking. Its absence destabilizes the non-catalytic subunits of the OST complex, resulting in decreased abundance of acrosomal membrane proteins and impaired sperm-egg fusion.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Plant Sciences
Wei Deng, Yun Ling Xie, Hui Qiao Tian, Xue Yi Zhu
Summary: This article discusses the early changes that occur in the fused egg of higher plants before the fusion of the nuclei of male and female gametes, especially the unknown egg cell proteins responsible for sperm-egg recognition, attachment, and fusion.
CRITICAL REVIEWS IN PLANT SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Xiaocui Zheng, Yiran Li, Tongxiao Cui, Jing Yang, Xiangfeng Meng, Haiqi Wang, Liusheng Chen, Jian He, Nan Chen, Liying Meng, Lin Ding, Ran Xie
Summary: Executing precise glycan editing is crucial for understanding glycan-related biological processes and improving disease therapy. This study introduces a versatile and traceless glycan modification method that allows customization of targeted protein glycoforms through chemical and photoregulation. The method minimizes interference and enables precise temporal control of editing events.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Cell Biology
Katherine A. Maniates, Andrew Singson
Summary: Complementary forward and reverse genetic approaches have led to a recent surge in the discovery of fertilization genes in various model systems. The number of genetically validated gamete surface molecules has more than doubled in the past few years, with all sperm fertilization genes encoding transmembrane or secreted molecules. However, the discovery of genes encoding oocyte molecules has lagged behind. This review discusses potential experimental biases and biological reasons that may have hindered the identification of egg fertilization genes, as well as current strategies to overcome these obstacles.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Alberto M. Rivera, Willie J. Swanson
Summary: Gene duplication and repeat domain expansions play an important role in the evolution of fertilization proteins, with gene duplication often facilitating the cooption of molecules into fertilization function and repeat domain expansions providing opportunities for the evolution of novel fertilization proteins.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Vipul Batra, Vanya Bhushan, Syed Azmal Ali, Parul Sarwalia, Ankit Pal, Seema Karanwal, Subhash Solanki, Arumugam Kumaresan, Rakesh Kumar, Tirtha Kumar Datta
Summary: The study identified over 300 proteins on the ejaculated buffalo sperm surface, most of which were extracellular and involved in immune or reproductive processes. Flow cytometry with six FITC-labelled lectins confirmed glycosylation of these proteins, and various beta-defensins including BuBD-129 and 126 were identified on the sperm surface. The findings suggest that buffalo spermatozoa are heavily glycosylated and that BuBDs may play a role in sperm function and male fertility regulation.
Article
Multidisciplinary Sciences
Chih-Lan Lin, Mirat Sojitra, Eric J. Carpenter, Ellen S. Hayhoe, Susmita Sarkar, Elizabeth A. Volker, Chao Wang, Duong T. Bui, Loretta Yang, John S. Klassen, Peng Wu, Matthew S. Macauley, Todd L. Lowary, Ratmir Derda
Summary: This study demonstrates the chemoenzymatic synthesis of a genetically-encoded liquid glycan array (LiGA) of complex type N-glycans on phage. The LiGA facilitates rigorous characterization of N-glycan structure and density using MALDI-TOF MS, and enables the identification of optimal structure/density combinations for recognition by glycan-binding proteins (GBPs). Injection of the LiGA into mice also helps identify glycoconjugates with structures and avidity necessary for enrichment in specific organs.
NATURE COMMUNICATIONS
(2023)
Review
Environmental Sciences
Jacqueline L. Padilla-Gamino, Lindsay Alma, Laura H. Spencer, Yaamini R. Venkataraman, Leah Wessler
Summary: This article reviews the impact of ocean acidification on sexual reproduction processes in marine invertebrates, and emphasizes the current research gaps. The analysis shows that ocean acidification decreases fertilization rates, but the sensitivity to pH changes varies among different taxa.
FRONTIERS IN MARINE SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Patrick Pilak, Andre Schiefner, Judith Seiboth, Johannes Oehrlein, Arne Skerra
Article
Biochemistry & Molecular Biology
Friedrich-Christian Deuschle, Andre Schiefner, Corinna Brandt, Arne Skerra
Article
Biochemical Research Methods
Andre Schiefner, Rebecca Walser, Michaela Gebauer, Arne Skerra
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2020)
Review
Biotechnology & Applied Microbiology
Friedrich-Christian Deuschle, Elena Ilyukhina, Arne Skerra
Summary: Anticalin proteins are engineered versions of lipocalins that form a new class of clinical-stage biopharmaceuticals. Through combinatorial gene libraries and molecular selection techniques, the natural ligand specificities of lipocalins have been expanded from small molecules to peptides and proteins, leading to the development of promising Anticalin lead candidates in various disease areas. Anticalins offer an alternative to antibodies with potentially superior features as next-generation biologics, with examples of drug candidates under preclinical and clinical development.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2021)
Article
Hematology
Marco Mannes, Arthur Dopler, Oliver Zolk, Sophia J. Lang, Rebecca Halbgebauer, Britta Hoechsmann, Arne Skerra, Christian K. Braun, Markus Huber-Lang, Hubert Schrezenmeier, Christoph Q. Schmidt
Summary: Use of C5 inhibitor eculizumab to block the terminal complement pathway has revolutionized clinical management of complement-mediated diseases. New findings show that C3/C5 convertases function differently than previously thought, with C3 inhibition not necessarily leading to C5 inhibition. Surface-deposited C4b alone can recruit and activate C5, and only C5 bound on C3b/C4b-decorated surfaces requires surface fixation for activation.
Article
Biochemistry & Molecular Biology
Uli Binder, Arne Skerra
Summary: This study successfully developed a long-acting version of Tα1, which effectively improves its plasma half-life in vivo, laying the foundation for the therapeutic development of the next generation of thymosin alpha 1. By combining PASylation technology with RimJ enzyme-mediated N-acetylation, the problems of stability, protein degradation, and low bioactivity of synthetic peptide drugs were addressed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Andreas Eichinger, Irmgard Neumaier, Arne Skerra
Summary: Bovine butyrophilin (BTN1A1) is a glycoprotein found on milk fat globules that acts as a hydrophilic coat protein. Its structure differs from human immune receptors but shows similarity to human myelin oligodendrocyte glycoprotein. This discovery may provide insights into the correlation between neurological autoimmune diseases and cow milk consumption.
BIOLOGICAL CHEMISTRY
(2021)
Article
Oncology
Caroline Werner, Stefan Stangl, Lukas Salvermoser, Melissa Schwab, Maxim Shevtsov, Alexia Xanthopoulos, Fei Wang, Ali Bashiri Dezfouli, Dennis Tholke, Christian Ostheimer, Daniel Medenwald, Martin Windberg, Matthias Bache, Martin Schlapschy, Arne Skerra, Gabriele Multhoff
Summary: Tumor-specific biomarkers, such as Hsp70 in liquid biopsies, are useful for tumor detection, monitoring of responses, and outcome prediction. The compHsp70 ELISA, using two monoclonal antibodies, is a sensitive and reliable tool for measuring free and vesicular Hsp70 levels in tumor patients' circulation, serving as a potential biomarker for risk assessment and therapeutic monitoring.
Article
Chemistry, Multidisciplinary
Jonas Schilz, Charlotte Clement, Franziska Greiner, Arne Skerra
Summary: A novel strategy for the efficient and gentle affinity purification of PASylated proteins is reported, which allows direct one-step purification from cell extracts or culture supernatants while avoiding harsh elution conditions. This method can improve the efficiency of biological drug development.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Andreas Eichinger, Sabine Rauth, Dominik Hinz, Anna Feuerbach, Arne Skerra
Summary: In this study, the structural analysis of two Anticalin(R) proteins that tightly bind A beta(40) peptide, a key player in Alzheimer's disease, were described. These proteins, engineered based on human lipocalin 2, show compact single-domain binding properties and offer a potential alternative to antibodies. Both crystal structures of the engineered anticalins revealed their ability to recognize the same epitope in the middle of the beta-amyloid peptide. This finding suggests that anticalins may play a significant role in the pathophysiology of Alzheimer's disease.
BIOLOGICAL CHEMISTRY
(2022)
Article
Gastroenterology & Hepatology
Anita Annahazi, Thomas Erwin Berger, Ihsan Ekin Demir, Florian Zeller, Michael Muller, Markus Anneser, Arne Skerra, Klaus Michel, Michael Schemann
Summary: This study demonstrated for the first time the presence of functional 5-HT1P receptors on human submucous neurons and found no evidence for a role of 5-HT4 or 5-HT7 receptors in the postsynaptic activation of human submucous neurons by 5-HT.
NEUROGASTROENTEROLOGY AND MOTILITY
(2022)
Article
Biochemistry & Molecular Biology
Laura Job, Anja Kohler, Andreas Eichinger, Mauricio Testanera, Benjamin Escher, Franz Worek, Arne Skerra
Summary: Neurotoxic organophosphorus compounds (OPs) can be extremely dangerous when misused. A potential treatment involves using an enzyme to break down the nerve agent into harmless substances. The bacterium Brevundimonas diminuta (BdPTE) has been studied for its potential in this area. Engineering studies have led to improved versions of BdPTE with high catalytic efficiency. Unexpectedly, the crystal structure of a highly active variant revealed a new conformation in the active site region, leading to further amino acid exchanges and optimization of the enzyme for OP nerve agent detoxification.
Article
Biochemistry & Molecular Biology
Lea Naestle, Friedrich-Christian Deuschle, Volker Morath, Arne Skerra
Summary: The transferrin receptor (TfR) plays a role in transporting substances across the blood-brain barrier, offering a non-invasive way to deliver therapeutics to the brain. Researchers have identified a specific lipocalin, called FerryCalin, which binds to murine TfR and shows potential as a vehicle for delivering biopharmaceuticals to the brain. Through affinity maturation, lipocalin variants were engineered to bind to TfR in a non-competitive manner, with FerryCalin exhibiting a dissociation constant of 3.8 nM. This research provides insight into the potential use of FerryCalin or its mutants for brain drug delivery.
Article
Biochemical Research Methods
Elena Jerschke, Andreas Eichinger, Arne Skerra
Summary: Using Anticalin technology, a lipocalin protein named Colchicalin has been engineered with high affinity for the toxic plant alkaloid colchicine, offering potential as an antidote and for sensitive detection in biological samples. The crystal structure of unliganded Colchicalin and its complex with colchicine were compared, revealing significant rearrangements in four structurally variable loops. Upon binding to colchicine, a dramatic shift and side-chain flip occur in loop #3 and Phe71, respectively, creating space in the ligand pocket. These findings demonstrate a conformational adaptation mechanism similar to that observed in antibodies, highlighting the general similarity between antigen/ligand binding by immunoglobulins and lipocalins.
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Laura Job, Anja Koehler, Mauricio Testanera, Benjamin Escher, Franz Worek, Arne Skerra
Summary: In this study, the phosphotriesterase of Brevundimonas diminuta (BdPTE) was rationally engineered to improve its hydrolysis efficiency of malaoxon, a common pesticide metabolite. The mutant BdPTE(VRNVVLARY) showed significantly increased hydrolysis rate and improved properties including expression yield, thermal stability, and oxidation resistance. This mutant BdPTE could be a promising candidate for developing a biocatalytic antidote for the detoxification of common pesticides and related organophosphorus compounds.
PROTEIN ENGINEERING DESIGN & SELECTION
(2023)