|
1
|
Xu T, Cui Y, Qin S, Wang YC. Genome-wide analysis of lectins in cyanobacteria: from evolutionary mode to motif patterns. BMC Genomics 2023; 24:688. [PMID: 37974077 PMCID: PMC10655256 DOI: 10.1186/s12864-023-09790-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 11/06/2023] [Indexed: 11/19/2023] Open
Abstract
Lectins are glycoproteins that can bind to specific carbohydrates, and different lectin families exhibit different biological activities. They are also present in the cyanobacteria and many of them have shown excellent therapeutic effect, which deserve for bioprospecting. However, in comparison to those from terrestrial plants, the current knowledge on cyanobacterial lectins is very limited. To this end, genome-wide analyses were performed to find out their evolutionary mode and motif patterns in 316 genomes of representative taxa. In results, 196 putative cyanobacterial lectins were dig out and 105 of them were classified into known families. Seven lectins were found to be belonged to distinct two lectin families, and they may have the potential activities of both lectin families. Whereas no MFP-2, Chitin, and Nictaba family lectins were found. What's more, the Legume lectin-like lectin family was found to be the richest and most complex in cyanobacteria, which could be a main research direction for future cyanobacterial lectin bioprospecting and development. Our classification and prediction of cyanobacteria lectins is expected to provide assistance in the development of lectin-based medicine and provide solutions to the current thorny viral and tumor diseases in humans.
Collapse
Affiliation(s)
- Tongli Xu
- Shandong University of Traditional Chinese Medicine, Jinan, 250335, China
- Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China
| | - Yulin Cui
- Binzhou Medical University, Yantai, 264003, China
| | - Song Qin
- Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China.
- Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, China.
| | - Yin-Chu Wang
- Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai, 264003, China.
- Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, 266071, China.
- National Basic Science Data Center, Beijing, 100190, China.
| |
Collapse
|
|
2
|
Bezerra RP, Conniff AS, Uversky VN. Comparative study of structures and functional motifs in lectins from the commercially important photosynthetic microorganisms. Biochimie 2022; 201:63-74. [PMID: 35839918 DOI: 10.1016/j.biochi.2022.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 06/17/2022] [Accepted: 07/08/2022] [Indexed: 11/26/2022]
Abstract
Photosynthetic microorganisms, specifically cyanobacteria and microalgae, can synthesize a vast array of biologically active molecules, such as lectins, that have great potential for various biotechnological and biomedical applications. However, since the structures of these proteins are not well established, likely due to the presence of intrinsically disordered regions, our ability to better understand their functionality is hampered. We embarked on a study of the carbohydrate recognition domain (CRD), intrinsically disordered regions (IDRs), amino acidic composition, as well as and functional motifs in lectins from cyanobacteria of the genus Arthrospira and microalgae Chlorella and Dunaliella genus using a combination of bioinformatics techniques. This search revealed the presence of five distinctive CRD types differently distributed between the genera. Most CRDs displayed a group-specific distribution, except to C. sorokiniana possessing distinctive CRD probably due to its specific lifestyle. We also found that all CRDs contain short IDRs. Bacterial lectin of Arthrospira prokarionte showed lower intrinsic disorder and proline content when compared to the lectins from the eukaryotic microalgae (Chlorella and Dunaliella). Among the important functions predicted in all lectins were several specific motifs, which directly interacts with proteins involved in the cell-cycle control and which may be used for pharmaceutical purposes. Since the aforementioned properties of each type of lectin were investigated in silico, they need experimental confirmation. The results of our study provide an overview of the distribution of CRD, IDRs, and functional motifs within lectin from the commercially important microalgae.
Collapse
Affiliation(s)
- Raquel P Bezerra
- Department of Morphology and Animal Physiology, Federal Rural University of Pernambuco-UFRPE, Dom Manoel de Medeiros Ave, Recife, PE, 52171-900, Brazil.
| | - Amanda S Conniff
- Department of Medical Engineering, Morsani College of Medicine and College of Engineering, University of South Florida, Tampa, FL, 33612, USA.
| | - Vladimir N Uversky
- Department of Molecular Medicine and USF Health Byrd Alzheimer's Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, 33612, USA.
| |
Collapse
|
|
3
|
Nabi-Afjadi M, Heydari M, Zalpoor H, Arman I, Sadoughi A, Sahami P, Aghazadeh S. Lectins and lectibodies: potential promising antiviral agents. Cell Mol Biol Lett 2022; 27:37. [PMID: 35562647 PMCID: PMC9100318 DOI: 10.1186/s11658-022-00338-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 04/21/2022] [Indexed: 12/30/2022] Open
Abstract
In nature, lectins are widely dispersed proteins that selectively recognize and bind to carbohydrates and glycoconjugates via reversible bonds at specific binding sites. Many viral diseases have been treated with lectins due to their wide range of structures, specificity for carbohydrates, and ability to bind carbohydrates. Through hemagglutination assays, these proteins can be detected interacting with various carbohydrates on the surface of cells and viral envelopes. This review discusses the most robust lectins and their rationally engineered versions, such as lectibodies, as antiviral proteins. Fusion of lectin and antibody’s crystallizable fragment (Fc) of immunoglobulin G (IgG) produces a molecule called a “lectibody” that can act as a carbohydrate-targeting antibody. Lectibodies can not only bind to the surface glycoproteins via their lectins and neutralize and clear viruses or infected cells by viruses but also perform Fc-mediated antibody effector functions. These functions include complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cell-mediated phagocytosis (ADCP). In addition to entering host cells, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein S1 binds to angiotensin-converting enzyme 2 (ACE2) and downregulates it and type I interferons in a way that may lead to lung disease. The SARS-CoV-2 spike protein S1 and human immunodeficiency virus (HIV) envelope are heavily glycosylated, which could make them a major target for developing vaccines, diagnostic tests, and therapeutic drugs. Lectibodies can lead to neutralization and clearance of viruses and cells infected by viruses by binding to glycans located on the envelope surface (e.g., the heavily glycosylated SARS-CoV-2 spike protein).
Collapse
Affiliation(s)
- Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran
| | - Morteza Heydari
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran, 13145-1384, Iran
| | - Hamidreza Zalpoor
- Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,American Association of Kidney Patients, Tampa, FL, USA
| | - Ibrahim Arman
- Department of Molecular Biology and Genetics, Faculty of Sciences and Arts, Zonguldak Bulent Ecevit University, Zonguldak, Turkey
| | - Arezoo Sadoughi
- Department of Immunology, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Parisa Sahami
- Medical Biology Research Center, Health Technologies Institute, Kermanshah University of Medical Sciences (KUMS), Kermanshah, Iran
| | - Safiyeh Aghazadeh
- Division of Biochemistry, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, 5756151818, Iran.
| |
Collapse
|
|
4
|
Antiviral Cyanometabolites-A Review. Biomolecules 2021; 11:biom11030474. [PMID: 33810129 PMCID: PMC8004682 DOI: 10.3390/biom11030474] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 03/19/2021] [Accepted: 03/20/2021] [Indexed: 12/14/2022] Open
Abstract
Global processes, such as climate change, frequent and distant travelling and population growth, increase the risk of viral infection spread. Unfortunately, the number of effective and accessible medicines for the prevention and treatment of these infections is limited. Therefore, in recent years, efforts have been intensified to develop new antiviral medicines or vaccines. In this review article, the structure and activity of the most promising antiviral cyanobacterial products are presented. The antiviral cyanometabolites are mainly active against the human immunodeficiency virus (HIV) and other enveloped viruses such as herpes simplex virus (HSV), Ebola or the influenza viruses. The majority of the metabolites are classified as lectins, monomeric or dimeric proteins with unique amino acid sequences. They all show activity at the nanomolar range but differ in carbohydrate specificity and recognize a different epitope on high mannose oligosaccharides. The cyanobacterial lectins include cyanovirin-N (CV-N), scytovirin (SVN), microvirin (MVN), Microcystisviridis lectin (MVL), and Oscillatoria agardhii agglutinin (OAA). Cyanobacterial polysaccharides, peptides, and other metabolites also have potential to be used as antiviral drugs. The sulfated polysaccharide, calcium spirulan (CA-SP), inhibited infection by enveloped viruses, stimulated the immune system’s response, and showed antitumor activity. Microginins, the linear peptides, inhibit angiotensin-converting enzyme (ACE), therefore, their use in the treatment of COVID-19 patients with injury of the ACE2 expressing organs is considered. In addition, many cyanobacterial extracts were revealed to have antiviral activities, but the active agents have not been identified. This fact provides a good basis for further studies on the therapeutic potential of these microorganisms.
Collapse
|
|
5
|
Tivey TR, Parkinson JE, Mandelare PE, Adpressa DA, Peng W, Dong X, Mechref Y, Weis VM, Loesgen S. N-Linked Surface Glycan Biosynthesis, Composition, Inhibition, and Function in Cnidarian-Dinoflagellate Symbiosis. MICROBIAL ECOLOGY 2020; 80:223-236. [PMID: 31982929 DOI: 10.1007/s00248-020-01487-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 01/08/2020] [Indexed: 06/10/2023]
Abstract
The success of symbioses between cnidarian hosts (e.g., corals and sea anemones) and micro-algal symbionts hinges on the molecular interactions that govern the establishment and maintenance of intracellular mutualisms. As a fundamental component of innate immunity, glycan-lectin interactions impact the onset of marine endosymbioses, but our understanding of the effects of cell surface glycome composition on symbiosis establishment remains limited. In this study, we examined the canonical N-glycan biosynthesis pathway in the genome of the dinoflagellate symbiont Breviolum minutum (family Symbiodiniaceae) and found it to be conserved with the exception of the transferase GlcNAc-TII (MGAT2). Using coupled liquid chromatography-mass spectrometry (LC-MS/MS), we characterized the cell surface N-glycan content of B. minutum, providing the first insight into the molecular composition of surface glycans in dinoflagellates. We then used the biosynthesis inhibitors kifunensine and swainsonine to alter the glycan composition of B. minutum. Successful high-mannose enrichment via kifunensine treatment resulted in a significant decrease in colonization of the model sea anemone Aiptasia (Exaiptasia pallida) by B. minutum. Hybrid glycan enrichment via swainsonine treatment, however, could not be confirmed and did not impact colonization. We conclude that functional Golgi processing of N-glycans is critical for maintaining appropriate cell surface glycan composition and for ensuring colonization success by B. minutum.
Collapse
Affiliation(s)
- Trevor R Tivey
- Department of Integrative Biology, Oregon State University, Corvallis, OR, USA.
- Department of Entomology, Cornell University, Ithaca, NY, USA.
| | - John Everett Parkinson
- Department of Integrative Biology, Oregon State University, Corvallis, OR, USA
- Department of Integrative Biology, University of South Florida, Tampa, FL, USA
| | - Paige E Mandelare
- Department of Chemistry, Oregon State University, Corvallis, OR, USA
- Whitney Laboratory for Marine Bioscience and Department of Chemistry, University of Florida, St. Augustine, FL, USA
| | - Donovon A Adpressa
- Department of Chemistry, Oregon State University, Corvallis, OR, USA
- Analytical Research & Development, Merck & Co. Inc., Boston, MA, USA
| | - Wenjing Peng
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA
| | - Xue Dong
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA
| | - Yehia Mechref
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA
| | - Virginia M Weis
- Department of Integrative Biology, Oregon State University, Corvallis, OR, USA
| | - Sandra Loesgen
- Department of Chemistry, Oregon State University, Corvallis, OR, USA.
- Whitney Laboratory for Marine Bioscience and Department of Chemistry, University of Florida, St. Augustine, FL, USA.
| |
Collapse
|
|
6
|
Molejon MI, Weiz G, Breccia JD, Vaccaro MI. Glycoconjugation: An approach to cancer therapeutics. World J Clin Oncol 2020; 11:110-120. [PMID: 32257842 PMCID: PMC7103525 DOI: 10.5306/wjco.v11.i3.110] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 01/31/2020] [Accepted: 02/08/2020] [Indexed: 02/06/2023] Open
Abstract
Cancer constitutes the second leading cause of death globally and is considered to have been responsible for an estimated 9.6 million fatalities in 2018. Although treatments against gastrointestinal tumors have recently advanced, those interventions can only be applied to a minority of patients at the time of diagnosis. Therefore, new therapeutic options are necessary for advanced stages of the disease. Glycosylation of antitumor agents, has been found to improve pharmacokinetic parameters, reduce side effects, and expand drug half-life in comparison with the parent compounds. In addition, glycosylation of therapeutic agents has been proven to be an effective strategy for their targeting tumor tissue, thereby reducing the doses of the glycodrugs administered to patients. This review focusses on the effect of the targeting properties of glycosylated antitumor agents on gastrointestinal tumors.
Collapse
Affiliation(s)
- Maria I Molejon
- Institute of Earth and Environmental Sciences from La Pampa (INCITAP), National University of La Pampa, School of Natural Sciences (CONICET-UNLPam), Santa Rosa 6300, La Pampa, Argentina
- Institute of Biochemistry and Molecular Medicine (UBA-CONICET), Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires C1113AAD, Argentina
| | - Gisela Weiz
- Institute of Earth and Environmental Sciences from La Pampa (INCITAP), National University of La Pampa, School of Natural Sciences (CONICET-UNLPam), Santa Rosa 6300, La Pampa, Argentina
| | - Javier D Breccia
- Institute of Earth and Environmental Sciences from La Pampa (INCITAP), National University of La Pampa, School of Natural Sciences (CONICET-UNLPam), Santa Rosa 6300, La Pampa, Argentina
| | - Maria Ines Vaccaro
- Institute of Biochemistry and Molecular Medicine (UBA-CONICET), Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires C1113AAD, Argentina
| |
Collapse
|
|
7
|
Mitchell CA, Ramessar K, O'Keefe BR. Antiviral lectins: Selective inhibitors of viral entry. Antiviral Res 2017; 142:37-54. [PMID: 28322922 PMCID: PMC5414728 DOI: 10.1016/j.antiviral.2017.03.007] [Citation(s) in RCA: 111] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Accepted: 03/13/2017] [Indexed: 01/27/2023]
Abstract
Many natural lectins have been reported to have antiviral activity. As some of these have been put forward as potential development candidates for preventing or treating viral infections, we have set out in this review to survey the literature on antiviral lectins. The review groups lectins by structural class and class of source organism we also detail their carbohydrate specificity and their reported antiviral activities. The review concludes with a brief discussion of several of the pertinent hurdles that heterologous proteins must clear to be useful clinical candidates and cites examples where such studies have been reported for antiviral lectins. Though the clearest path currently being followed is the use of antiviral lectins as anti-HIV microbicides via topical mucosal administration, some investigators have also found systemic efficacy against acute infections following subcutaneous administration.
Collapse
Affiliation(s)
- Carter A Mitchell
- Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD, 21702-1201, USA
| | - Koreen Ramessar
- Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD, 21702-1201, USA
| | - Barry R O'Keefe
- Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD, 21702-1201, USA.
| |
Collapse
|
|
8
|
Wang Y, Gao J, Gu G, Li G, Cui C, Sun B, Lou H. In situ RBL receptor visualization and its mediated anticancer activity for solasodine rhamnosides. Chembiochem 2011; 12:2418-20. [PMID: 21953983 DOI: 10.1002/cbic.201100551] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2011] [Indexed: 12/11/2022]
Affiliation(s)
- Yanyan Wang
- Department of Natural Products Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan, China
| | | | | | | | | | | | | |
Collapse
|
|
9
|
Shahzad-ul-Hussan S, Gustchina E, Ghirlando R, Clore GM, Bewley CA. Solution structure of the monovalent lectin microvirin in complex with Man(alpha)(1-2)Man provides a basis for anti-HIV activity with low toxicity. J Biol Chem 2011; 286:20788-96. [PMID: 21471192 PMCID: PMC3121468 DOI: 10.1074/jbc.m111.232678] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2011] [Revised: 03/23/2011] [Indexed: 11/06/2022] Open
Abstract
Lectins that bind surface envelope glycoprotein gp120 of HIV with high avidity can potently inhibit viral entry. Yet properties such as multivalency that facilitate strong interactions can also cause nonspecific binding and toxicity. The cyanobacterial lectin microvirin (MVN) is unusual as it potently inhibits HIV-1 with negligible toxicity compared with cyanovirin-N (CVN), its well studied antiviral homolog. To understand the structural and mechanistic basis for these differences, we solved the solution structure of MVN free and in complex with its ligand Manα(1-2)Man, and we compared specificity and time windows of inhibition with CVN and Manα(1-2)Man-specific mAb 2G12. We show by NMR and analytical ultracentrifugation that MVN is monomeric in solution, and we demonstrate by NMR that Manα(1-2)Man-terminating carbohydrates interact with a single carbohydrate-binding site. Synchronized infectivity assays show that 2G12, MVN, and CVN inhibit entry with distinct kinetics. Despite shared specificity for Manα(1-2)Man termini, combinations of the inhibitors are synergistic suggesting they recognize discrete glycans and/or dynamic glycan conformations on gp120. Entry assays employing amphotropic viruses show that MVN is inactive, whereas CVN potently inhibits both. In addition to demonstrating that HIV-1 can be inhibited through monovalent interactions, given the similarity of the carbohydrate-binding site common to MVN and CVN, these data suggest that gp120 behaves as a clustered glycan epitope and that multivalent-protein interactions achievable with CVN but not MVN are required for inhibition of some viruses.
Collapse
Affiliation(s)
| | | | - Rodolfo Ghirlando
- the Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892
| | | | | |
Collapse
|
|
10
|
Roldós V, Cañada FJ, Jiménez-Barbero J. Carbohydrate-Protein Interactions: A 3D View by NMR. Chembiochem 2011; 12:990-1005. [DOI: 10.1002/cbic.201000705] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2010] [Indexed: 12/29/2022]
|
|
11
|
Sato Y, Hirayama M, Morimoto K, Yamamoto N, Okuyama S, Hori K. High mannose-binding lectin with preference for the cluster of alpha1-2-mannose from the green alga Boodlea coacta is a potent entry inhibitor of HIV-1 and influenza viruses. J Biol Chem 2011; 286:19446-58. [PMID: 21460211 DOI: 10.1074/jbc.m110.216655] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
The complete amino acid sequence of a lectin from the green alga Boodlea coacta (BCA), which was determined by a combination of Edman degradation of its peptide fragments and cDNA cloning, revealed the following: 1) B. coacta used a noncanonical genetic code (where TAA and TAG codons encode glutamine rather than a translation termination), and 2) BCA consisted of three internal tandem-repeated domains, each of which contains the sequence motif similar to the carbohydrate-binding site of Galanthus nivalis agglutinin-related lectins. Carbohydrate binding specificity of BCA was examined by a centrifugal ultrafiltration-HPLC assay using 42 pyridylaminated oligosaccharides. BCA bound to high mannose-type N-glycans but not to the complex-type, hybrid-type core structure of N-glycans or oligosaccharides from glycolipids. This lectin had exclusive specificity for α1-2-linked mannose at the nonreducing terminus. The binding activity was enhanced as the number of terminal α1-2-linked mannose substitutions increased. Mannobiose, mannotriose, and mannopentaose were incapable of binding to BCA. Thus, BCA preferentially recognized the nonreducing terminal α1-2-mannose cluster as a primary target. As predicted from carbohydrate-binding propensity, this lectin inhibited the HIV-1 entry into the host cells at a half-maximal effective concentration of 8.2 nm. A high association constant (3.71 × 10(8) M(-1)) of BCA with the HIV envelope glycoprotein gp120 was demonstrated by surface plasmon resonance analysis. Moreover, BCA showed the potent anti-influenza activity by directly binding to viral envelope hemagglutinin against various strains, including a clinical isolate of pandemic H1N1-2009 virus, revealing its potential as an antiviral reagent.
Collapse
Affiliation(s)
- Yuichiro Sato
- Faculty of Pharmacy, Yasuda Women's University, Asaminami, Hiroshima, Japan
| | | | | | | | | | | |
Collapse
|