Article
Medicine, Research & Experimental
Yahui Wen, Feiyan Shen, Haibin Wu
Summary: The study revealed the important roles of C5a and C5aR in cardiomyocyte senescence, and suggested that a C5aR antagonist may be an effective method for preventing DOX-induced cardiomyocyte aging.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Richa Mishra, Aurosikha Das, Soumendra Rana
Summary: Resveratrol, a promiscuous phytoalexin found in fruits and nuts, exhibits health benefits through antioxidant and anti-inflammatory activities. It directly binds to COX-1, COX-2 enzymes, and (h)C5a, modulating inflammatory pathways and showing anti-inflammatory effects.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Multidisciplinary Sciences
Yu-Qi Ping, Chunyou Mao, Peng Xiao, Ru-Jia Zhao, Yi Jiang, Zhao Yang, Wen-Tao An, Dan-Dan Shen, Fan Yang, Huibing Zhang, Changxiu Qu, Qingya Shen, Caiping Tian, Zi-Jian Li, Shaolong Li, Guang-Yu Wang, Xiaona Tao, Xin Wen, Ya-Ni Zhong, Jing Yang, Fan Yi, Xiao Yu, H. Eric Xu, Yan Zhang, Jin-Peng Sun
Summary: This study reveals how glucocorticoid stress hormones activate adhesion GPCR G3 and how glucocorticoids bind to its transmembrane domain, triggering receptor activation. The research also found that GPR97's cytoplasmic side has an open cavity where interactions with the Go protein contribute to its high basal activity.
Article
Immunology
Sokratis A. Apostolidis, Amrita Sarkar, Heather M. Giannini, Rishi R. Goel, Divij Mathew, Aae Suzuki, Amy E. Baxter, Allison R. Greenplate, Cecile Alanio, Mohamed Abdel-Hakeem, Derek A. Oldridge, Josephine R. Giles, Jennifer E. Wu, Zeyu Chen, Yinghui Jane Huang, Jonathan Belman, Ajinkya Pattekar, Sasikanth Manne, Oliva Kuthuru, Jeanette Dougherty, Brittany Weiderhold, Ariel R. Weisman, Caroline A. G. Ittner, Sigrid Gouma, Debora Dunbar, Ian Frank, Alexander C. Huang, Laura A. Vella, John P. Reilly, Scott E. Hensley, Lubica Rauova, Liang Zhao, Nuala J. Meyer, Mortimer Poncz, Charles S. Abrams, E. John Wherry
Summary: Patients with severe COVID-19 exhibit higher levels of platelet activation, which is associated with poor clinical outcomes and thrombotic events. Plasma from COVID-19 patients activates platelets from healthy donors and is correlated with kidney and liver injury. Blocking certain signaling pathways reverses this platelet hyperactivity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Monika Bednarczyk, Carolina Medina-Montano, Frederic Julien Fittler, Henner Stege, Meike Roskamp, Michael Kuske, Christian Langer, Marco Vahldieck, Evelyn Montermann, Ingrid Tubbe, Nadine Roehrig, Andrzej Dzionek, Stephan Grabbe, Matthias Bros
Summary: The development of nanocarriers for biomedical applications is of great interest due to their potential to deliver drugs in a targeted manner. This study demonstrates that carbohydrate-coated nanocarriers trigger immune responses and exhibit enhanced binding to cells when complement-opsonized.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Danyu You, Mengjie Weng, Xiaoting Wu, Kun Nie, Jiong Cui, Yi Chen, Liyan Yang, Jianxin Wan
Summary: This study aimed to elucidate the roles of C3aR and the NLRP3 inflammasome in unilateral ureteral obstruction (UUO)-induced renal interstitial fibrosis. The findings showed that C3aR deficiency improved renal function and attenuated renal fibrosis and NLRP3 inflammasome activation in UUO mice. Inhibition of the NLRP3 inflammasome also resulted in attenuated renal function and fibrosis in UUO mice.
Article
Fisheries
Bo Jiang, Zhenhua Zhang, Jian Xu, Huan Jin, Tuya, Yongqing Li
Summary: C3d is an important protein in the immune system, connecting innate and adaptive immunity. Phylogenetic and structural analyses show that some wild birds have C3d proteins with characteristics closer to mammals, potentially leading to stronger immunity against pathogens.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Michael Overduin, Catharine Trieber, R. Scott Prosser, Louis-Philippe Picard, Joey G. Sheff
Summary: Membrane proteins play essential roles in biological structures within asymmetric lipid bilayers. The use of native nanodiscs formed with specific copolymers allows for extraction of these proteins directly from diverse cell and organelle membranes. Understanding the interactions between transmembrane targets and lipids is crucial for the development of next-generation native nanodiscs with therapeutic applications.
Article
Biochemistry & Molecular Biology
Liangliang Mu, Li Qiu, Jiadong Li, Hao Bai, Yang Lei, Qingliang Zeng, Lili Wang, Weiwei Qi, Xiaoxue Yin, Jianmin Ye
Summary: This study explores the role of complement component 9 (C9) in the immune response of tilapia fish to bacterial infection. The study found that the expression of OnC9 was significantly changed upon infection and knockdown of OnC9 led to rapid proliferation of pathogenic bacteria and fish death. However, the phenotype was rescued by re-injection of OnC9. The study also reveals that OnC9 is involved in complement-mediated cell lysis and is associated with OnCD59 to regulate the efficiency of lysis.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Multidisciplinary Sciences
Nadia Sukusu Nielsen, Alessandra Zarantonello, Seandean Lykke Harwood, Kathrine Tejlgard Jensen, Katarzyna Kjoge, Ida B. Thogersen, Leif Schauser, Jesper Lykkegaard Karlsen, Gregers R. Andersen, Jan J. Enghild
Summary: This study investigates the protease-inhibitory mechanism of human A2ML1 and determines the structures of its native and protease-cleaved conformations. The functional unit of A2ML1 is a monomer that depends on covalent binding of the protease to achieve inhibition. Structural analysis shows that disruption of the bait region triggers conformational changes, resulting in protease inhibition.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Weiwei Ji, Qi Peng, Xueqiong Fang, Zehou Li, Yaxin Li, Cunfa Xu, Shuqing Zhao, Jizong Li, Rong Chen, Guoxiang Mo, Zhanyong Wei, Ying Xu, Bin Li, Shuijun Zhang
Summary: Researchers have reported the structures of porcine deltacoronavirus (PDCoV) spike protein bound to aminopeptidase receptors in pigs and humans, shedding light on the potential mechanism of cross-species transmission of the virus. The study found that PDCoV can infect various animals and humans, using aminopeptidase N from different host species as receptors to enter cells. The detailed mechanism of how PDCoV recognizes homologous receptors and insights into the cross-species transmission of the virus were provided.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ikko Nureki, Kazuhiro Kobayashi, Tatsuki Tanaka, Kanae Demura, Asuka Inoue, Wataru Shihoya, Osamu Nureki
Summary: This study reported the cryoelectron microscopy structures of beta(3)-adrenergic receptor (beta(3)AR) in complex with selective agonist solabegron and nonselective agonist isoproterenol. The structural analysis revealed the conformational changes of extracellular loop 2 depending on the bound agonist and the narrow exosite of beta(3)AR, which explains the receptor's preference for specific agonists with elongated shapes. This study deepens the understanding of beta(3)AR agonist binding characteristics and has implications for the development of selective drugs.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Immunology
Anne Landsem, Ase Emblem, Corinna Lau, Dorte Christiansen, Alexandra Gerogianni, Bard Ove Karlsen, Tom Eirik Mollnes, Per H. H. Nilsson, Ole-Lars Brekke
Summary: In this study, the role of complement in E. coli-induced platelet aggregation in human whole blood was investigated. The researchers found that compstatin, an inhibitor of complement component C3 cleavage, reduced E. coli-induced platelet aggregation. Contrary to previous belief, the aggregation was not C3a-mediated but rather dependent on C3b. Glycoprotein IIb/IIIa and complement receptor 1 (CR1) were also found to be involved in the aggregation process. These findings provide insights into the mechanism of platelet aggregation regulated by complement in bacterial infections.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Akihiro Kawamoto, Tomohito Yamada, Toru Yoshida, Yusui Sato, Takayuki Kato, Hideaki Tsuge
Summary: Some bacteria have a toxin delivery system that transports enzymes into host cells. The bacterium Clostridioides difficile has a clinically important system with CDTa and CDTb proteins as therapeutic targets. The cryo-EM structure of CDTa bound to CDTb-pore was reported, revealing structural changes induced by CDTa binding and the involvement of an NSS-loop in substrate translocation. The dynamic information obtained provides insights for drug design against hypervirulent C. difficile strains.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Marion Anliker-Ort, Jasper Dingemanse, Herve Farine, Peter Groenen, Ruediger Kornberger, John van den Anker, Priska Kaufmann
Summary: This study aimed to investigate the safety, tolerability, pharmacokinetics, and target engagement of multiple-ascending doses of ACT-1014-6470. The results showed that the compound was generally safe and well tolerated at all dose levels, with sustained target engagement.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Richa Mishra, Soumendra Rana
BIOORGANIC & MEDICINAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Richa Mishra, Aurosikha Das, Soumendra Rana
Summary: Resveratrol, a promiscuous phytoalexin found in fruits and nuts, exhibits health benefits through antioxidant and anti-inflammatory activities. It directly binds to COX-1, COX-2 enzymes, and (h)C5a, modulating inflammatory pathways and showing anti-inflammatory effects.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Richa Mishra, Lalita Mohan Behera, Soumendra Rana
Summary: hC5a, as a pro-inflammatory glycoprotein, plays an important role in drug research. Recent studies have shown that hC5a can cooperatively accommodate drugs at multiple sites, suggesting exploration of polypharmacology for targeting inflammatory diseases related to the "cytokine storm".
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Multidisciplinary
Aurosikha Das, Lalita Mohan Behera, Soumendra Rana
Summary: This study provides biophysical validation of the hypothesized two-site binding interactions of C5a with C5aR1, improving understanding of the physiological and pathological roles of the complement system. The findings may advance the development of new-generation antibodies and neutraligands targeting C5a for modulating its interaction with C5aR1.
Article
Biochemistry & Molecular Biology
Lalita Mohan Behera, Manaswini Ghosh, Soumendra Rana
Summary: Amino acids play important roles in the synthesis of both synthetic and natural peptides, and mapping protein-protein interactions using chemical biology approaches provides pharmacologically relevant peptides. Over 60 peptide-based drugs have been approved, and more peptides are currently in clinical trials. However, the pharmacological properties of natural peptides often need to be fine-tuned by replacing amino acids with non-coded amino acids. This study explores the conformational landscape of several C alpha-substituted aromatic non-coded amino acids and provides insights for the rational design of optimized peptide sequences with potent biological activities.
Article
Biochemistry & Molecular Biology
Aurosikha Das, Pulkit K. Gupta, Soumendra Rana
Summary: C5a, a potent proinflammatory glycoprotein, interacts with receptors C5aR1 and C5aR2, with the latter potentially having a context-dependent functional relevance compared to the extensively studied C5aR1. The structure of C5aR2 and its specificity towards C5a remain elusive, but efforts to refine model structures and molecular dynamics data aim to enhance understanding of C5a-C5aR2 interaction for further elucidating the debated biological function of C5aR2 in the future.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Aurosikha Das, Manaswini Ghosh, Pulkit Kr. Gupta, Soumendra Rana
Summary: The complement system is crucial in immune response and plays an important role in physiology and pathophysiology. C5a, one of the most potent anaphylatoxins, triggers pro-inflammatory responses by binding to complement receptors. Targeting C5a with small molecule drugs can potentially modulate its destructive signaling response under pathological conditions.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Review
Immunology
Manaswini Ghosh, Soumendra Rana
Summary: The complement system is an ancient host defense system that regulates the immune response. It acts as a bridge between innate and adaptive immunity. The complement system consists of various glycoproteins that control infection and inflammation. C5a is the most potent proinflammatory anaphylatoxin and plays a role in inflammatory signaling in different tissues. This review provides a comprehensive overview of human C5a, including its structure, signaling, and potential therapeutic applications.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lalita Mohan Behera, Manaswini Ghosh, Pulkit Kr. Gupta, Soumendra Rana
Summary: Antimicrobial resistance (AMR) requires urgent attention in the post-COVID world, and the development of new antimicrobial agents is limited. However, the design and engineering of synthetic AMPs show potential as therapeutic candidates to combat AMR.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Manaswini Ghosh, Sucharita Shadangi, Soumendra Rana
Summary: Human complement fragment 5a (C5a) is a potent glycoprotein involved in complement-mediated inflammation. Excessive interaction of C5a with its receptors is associated with chronic inflammatory diseases. This study explores the potential of designer peptides to mimic the function of antibodies and inhibit the interaction between C5a and its receptors. Computational data supports the effectiveness of the designed peptides, although further experimental studies are needed.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)