Article
Biology
Kaijun Chi, Huilin Xu, Hanjie Li, Ganglong Yang, Xiaoman Zhou, Xiao-Dong Gao
Summary: This study compared the adaptability and yield of expressing Siglec9-Fc fusion protein in HEK293 and CHO cell lines, and optimized the culture conditions. The glycosylation, yield, dimerization, and sialic acid binding activity of the Siglec9-Fc protein produced in HEK293 and CHO were analyzed. The study found that the protein yield was slightly higher in CHO compared to HEK293, and the recombinant protein from HEK293 had more fucosylation, while CHO showed more sialylation. Both products exhibited high dimerization ratio and sialic acid binding activity. Furthermore, the study analyzed the potential ligands on cancer cell lines and bladder cancer tissue. The results are important for selecting suitable Siglec9-Fc protein expression systems and detecting related ligands.
Article
Biochemistry & Molecular Biology
Hauke Thiesler, Julia Beimdiek, Herbert Hildebrandt
Summary: The release of microglia-intrinsic polySia pool inhibits the inflammatory response by acting as a trans-activating ligand of Siglec-E, as indicated in traumatic brain injury (TBI).
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sarah El Kharraz, Vanessa Dubois, Martin E. van Royen, Adriaan B. Houtsmuller, Ekatarina Pavlova, Nina Atanassova, Tien Nguyen, Arnout Voet, Roy Eerlings, Florian Handle, Stefan Prekovic, Elien Smeets, Lisa Moris, Wout Devlies, Claes Ohlsson, Matti Poutanen, Kevin J. Verstrepen, Geert Carmeliet, Kaisa-Mari Launonen, Laura Helminen, Jorma J. Palvimo, Claude Libert, Dirk Vanderschueren, Christine Helsen, Frank Claessens
Summary: Dimerization of the ligand-binding domain of the androgen receptor (AR) is crucial for transcriptional regulation and proper functioning of AR. Mutations disrupting LBD dimerization can lead to significant effects, as demonstrated in a mouse model in this study.
Article
Cell Biology
Philip Schmassmann, Julien Roux, Alicia Buck, Nazanin Tatari, Sabrina Hogan, Jinyu Wang, Natalia Rodrigues Mantuano, Ronja Wieboldt, Sohyon Lee, Berend Snijder, Deniz Kaymak, Tomas A. Martins, Marie-Francoise Ritz, Tala Shekarian, Marta McDaid, Michael Weller, Tobias Weiss, Heinz Laeubli, Gregor Hutter
Summary: This study found that high expression of sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is associated with reduced survival in patients with glioblastoma (GBM). Through specific knockouts of Siglec-E and single-cell RNA sequencing, the researchers demonstrated that Siglec-E inhibits phagocytosis by microglia- and monocyte-derived cells, promoting immune evasion. Loss of Siglec-E on monocyte-derived cells enhanced antigen cross-presentation and pro-inflammatory cytokine production, resulting in improved T cell priming. The combination of innate and adaptive immune responses delayed tumor growth and prolonged survival in murine models of GBM. Furthermore, the study showed the potential for targeting Siglec-9 as a treatment for GBM through the combination with other immunotherapies.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Khushbu Rauniyar, Soheila Akhondzadeh, Anna Gaciarz, Jaana Kunnapuu, Michael Jeltsch
Summary: This study successfully expressed biologically active VEGF-C in E. coli cells using two different methods, bypassing the need for in vitro folding for the first time. This provides a new approach and method for expressing VEGF-C using bacterial expression systems, potentially saving costs and time.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Joni Vuorio, Jana Skerlova, Milan Fabry, Vaclav Veverka, Ilpo Vattulainen, Pavlina Rezacova, Hector Martinez-Seara
Summary: This study reveals that CD44 receptor has multiple distinct binding sites for hyaluronan, which are modulated by N-glycosylation. Non-glycosylated CD44 prefers a canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan through a different micromolar binding site. The findings demonstrate how glycosylation can alter receptor affinity and emphasize the importance of considering glycosylation in protein function and structure determination.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Gyunghee Jo, Jeomil Bae, Ho Jeong Hong, Ah-reum Han, Do-Kyun Kim, Seon Pyo Hong, Jung A. Kim, Sangkyu Lee, Gou Young Koh, Ho Min Kim
Summary: Angiopoietin (Angpt)-Tie receptor 2 (Tie2) plays a key role in regulating vascular stability and is a potential therapeutic target in vascular diseases. A new Tie2-agonistic antibody has been developed, targeting a site distinct from the Angpt1-binding site, influencing Tie2 clustering and activation in an Angpt2 inhibition-resistant manner.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Laura E. Kilpatrick, Stephen J. Hill
Summary: Some G protein-coupled receptors (GPCRs) are not evenly expressed within the plasma membrane but may form distinct signaling microdomains, localizing GPCRs in close proximity with other membrane proteins and intracellular signaling partners. Techniques like fluorescence correlation spectroscopy (FCS) are needed for probing the molecular mechanisms governing GPCR pharmacology within these domains.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Chemistry, Medicinal
Horst Prescher, Astrid Schweizer, Martin Frank, Elena Kuhfeldt, Julia Ring, Lars Nitschke
Summary: The development of high affinity ligands for Siglecs is of significant interest due to their therapeutically relevant functions. This study introduces a new strategy for developing and designing Siglec ligands, using Siglec-2 (CD22) as an example, as disialyl-oligosaccharide mimetics. The study provides insights into the development and design of dimeric ligands with high affinity and avidity to cell surface-expressed CD22, as well as assay development, structure activity relationships, and biological data on calcium flux regulation in B-cells. State-of-the-art molecular dynamics simulations are used to model the binding modes of selected ligands, opening new perspectives for drug design efforts targeting Siglecs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Mingjie Xu, Lizhi Sun, Yan Wang, Shuchun Gao, Weihua Yang, Meng Li
Summary: This study investigated the effects of specific amino acid substitutions at position 562 of the hepatitis E virus (HEV) capsid protein pORF2 on its activity. The results showed that these substitutions play crucial roles in the neutralizing epitope activity, affecting glycosylation, antigenicity, immunogenicity, and neutralization activities of the virus.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Biophysics
Yihan Huang, Bradley S. Harris, Shiaki A. Minami, Seongwon Jung, Priya S. Shah, Somen Nandi, Karen A. McDonald, Roland Faller
Summary: Highly detailed steered molecular dynamics simulations were conducted on differently glycosylated receptor binding domains of the SARS-CoV-2 spike protein. Glycosylation increased the binding strength and range, and a catch-slip behavior was observed during protein pulling, where new interactions replaced broken interactions. Hydrogen bonds were the dominant interaction mode, while Lennard-Jones and electrostatic interactions were also relevant.
BIOPHYSICAL JOURNAL
(2022)
Article
Cell Biology
Quirin Hammer, Josefine Dunst, Wanda Christ, Francesca Picarazzi, Mareike Wendorff, Pouria Momayyezi, Oisin Huhn, Herman K. Netskar, Kimia T. Maleki, Marina Garcia, Takuya Sekine, Ebba Sohlberg, Valerio Azzimato, Myriam Aouadi, Frauke Degenhardt, Andre Franke, Francesco Spallotta, Mattia Mori, Jakob Michaelsson, Niklas K. Bjorkstrom, Timo Rueckert, Chiara Romagnani, Amir Horowitz, Jonas Klingstrom, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
Summary: A viral peptide encoded by the Non-structural protein 13 of SARS-CoV-2 prevents the binding of HLA-E to the inhibitory receptor NKG2A, leading to the activation of NK cells and their ability to limit viral replication. This finding provides insights into the immune response of NK cells against SARS-CoV-2 and its mechanisms.
Article
Cell Biology
Xiaoli Zhang, Xueting Wang, Ziyang Xu, Fengwei Sun, Yi Jia, Yue Tian
Summary: Activated microglia-induced inflammation in the hippocampus plays a crucial role in perioperative neurocognitive disorders. This study investigates the role of glycan ligand alteration on neurons in sevoflurane-induced neurocognitive disorders. The data shows that a decrease in Siglec-E ligand expression on neurons, induced by age and sevoflurane treatment, disrupts inflammatory homeostasis.
Article
Biochemistry & Molecular Biology
Jaesoo Jung, Jhon R. Enterina, Duong T. Bui, Fahima Mozaneh, Po-Han Lin, Nitin, Chu-Wei Kuo, Emily Rodrigues, Abhishek Bhattacherjee, Parisa Raeisimakiani, Gour C. Daskhan, Chris D. St Laurent, Kay-Hooi Khoo, Lara K. Mahal, Wesley F. Zandberg, Xuefei Huang, John S. Klassen, Matthew S. Macauley
Summary: The study shows that specific sulfate modifications can affect Siglec ligand binding and the results are cell type-dependent. The mechanism of carbohydrate sulfation in modulating Siglec ligands in cells can be utilized for immune evasion in cancer.
ACS CHEMICAL BIOLOGY
(2021)
Article
Polymer Science
Risa Naka, Simon Sau Yin Law, Ayaka Tateishi, Keiji Numata, Masashi Ohmae
Summary: Siglec-8, a lectin involved in suppressing allergic responses, is considered a therapeutic target for developing glycan materials that can regulate inflammatory diseases. This study investigated the relationship between the density of glycans and the avidity of interactions with Siglec-8. The results showed that Siglec-8 has an optimal glycan density for preferred interactions, and regulating glycan density is key to developing therapeutic materials targeting Siglec-8.
Article
Biochemistry & Molecular Biology
Melissa M. Matthews, John B. McArthur, Yanhong Li, Hai Yu, Xi Chen, Andrew J. Fisher
Article
Biochemistry & Molecular Biology
Yanhong Li, Riyao Li, Hai Yu, Xue Sheng, Jing Wang, Andrew J. Fisher, Xi Chen
Article
Food Science & Technology
Valerie Weinborn, Yanhong Li, Ishita M. Shah, Hai Yu, David C. Dallas, J. Bruce German, David A. Mills, Xi Chen, Daniela Barile
INTERNATIONAL DAIRY JOURNAL
(2020)
Article
Chemistry, Physical
Jiali Zhang, Hai Yu, Bradley Harris, Yunbo Zheng, Umit Celik, Lan Na, Roland Faller, Xi Chen, Dominik R. Haudenschild, Gang-yu Liu
JOURNAL OF PHYSICAL CHEMISTRY C
(2020)
Article
Virology
Karen N. Barnard, Brynn K. Alford-Lawrence, David W. Buchholz, Brian R. Wasik, Justin R. LaClair, Hai Yu, Rebekah Honce, Stefan Ruhl, Petar Pajic, Erin K. Daugherity, Xi Chen, Stacey L. Schultz-Cherry, Hector C. Aguilar, Ajit Varki, Colin R. Parrish
JOURNAL OF VIROLOGY
(2020)
Article
Virology
Runxia Liu, Chithra Sreenivasan, Hai Yu, Zizhang Sheng, Simon J. Newkirk, Wenfeng An, David F. Smith, Xi Chen, Dan Wang, Feng Li
Article
Chemistry, Physical
Riyao Li, Hai Yu, Saddam M. Muthana, Daron Freedberg, Xi Chen
Article
Microbiology
Tri Nguyen, Sohyoung Lee, Yi-An Yang, Changhwan Ahn, Ji Hyun Sim, Tiffany G. Kei, Karen N. Barnard, Hai Yu, Shawn K. Millano, Xi Chen, Colin R. Parrish, Jeongmin Song
Article
Chemistry, Physical
Lan Na, Hai Yu, John B. McArthur, Tamashree Ghosh, Thomas Asbell, Xi Chen
Article
Oncology
Ron Amon, Ronit Rosenfeld, Shahar Perlmutter, Oliver C. Grant, Sharon Yehuda, Aliza Borenstein-Katz, Ron Alcalay, Tal Marshanski, Hai Yu, Ron Diskin, Robert J. Woods, Xi Chen, Vered Padler-Karavani
Review
Biochemistry & Molecular Biology
Shoib Sarwar Siddiqui, Sofia Rahman, H. P. Vasantha Rupasinghe, Cijo George Vazhappilly
Article
Biochemistry & Molecular Biology
Libo Zhang, Hai Yu, Yuanyuan Bai, Bijoyananda Mishra, Xiaoxiao Yang, Jing Wang, Evan B. Yu, Riyao Li, Xi Chen
Summary: Carbohydrate-protein conjugates have diverse applications, from vaccines to high-throughput assays. A process combining chemoenzymatic synthesis, squarate linker conjugation, and neoglycoprotein immobilization on fluorescent magnetic beads was developed for a suspension multiplex array platform. This platform allowed for analysis of glycan and GBP interactions, providing useful insights into human galectins' multivalent glycan-binding properties.
Review
Biology
Seba Alsawaf, Fatema Alnuaimi, Saba Afzal, Rinku Mariam Thomas, Ayshwarya Lakshmi Chelakkot, Wafaa S. Ramadan, Rawad Hodeify, Rachel Matar, Maxime Merheb, Shoib Sarwar Siddiqui, Cijo George Vazhappilly
Summary: Flavonoids have shown nephroprotective effects by improving antioxidant status, reducing oxidative stress, and modulating inflammatory responses in the kidney. Although limited, clinical trials suggest that a diet rich in flavonoids could have beneficial outcomes for patients with kidney diseases.
Article
Biochemistry & Molecular Biology
Wanqing Li, Marcos D. Battistel, Hannah Reeves, Lisa Oh, Hai Yu, Xi Chen, Lee-Ping Wang, Daron Freedberg
Article
Chemistry, Organic
John B. McArthur, Abhishek Santra, Wanqing Li, Anoopjit S. Kooner, Ziqi Liu, Hai Yu, Xi Chen
ORGANIC & BIOMOLECULAR CHEMISTRY
(2020)