A5029043252- Complement system in diseases
- Monoclonal and Polyclonal Antibodies Research
- Herpesvirus Infections and Treatments
- Blood groups and transfusion
- Mosquito-borne diseases and control
- Glycosylation and Glycoproteins Research
- Poxvirus research and outbreaks
- Cytomegalovirus and herpesvirus research
- Erythrocyte Function and Pathophysiology
- Peptidase Inhibition and Analysis
- Leprosy Research and Treatment
- Virology and Viral Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Transgenic Plants and Applications
- Plant Virus Research Studies
- HIV Research and Treatment
- Viral-associated cancers and disorders
- Aquaculture disease management and microbiota
- Renal Diseases and Glomerulopathies
- Toxin Mechanisms and Immunotoxins
- Galectins and Cancer Biology
- Immune Cell Function and Interaction
- Respiratory viral infections research
- RNA modifications and cancer
- Antifungal resistance and susceptibility
Goulburn Valley Health
2022-2024
National Centre for Cell Science
2014-2023
Savitribai Phule Pune University
2003-2022
The University of Melbourne
2022
Nagaland University
2018
Symbiosis International University
2018
Dr. K.N.Modi University
2016
University of Pennsylvania
1996-2006
Bhabha Atomic Research Centre
2005
UiT The Arctic University of Norway
2000
We have screened a phage-displayed random peptide library for binding to C3b, the proteolytically activated form of complement component C3, and identified novel that suppresses activation. This bound C3c, but not C3d, indicating it binds C3c region C3. A synthetic 27-amino acid corresponding also C3 fragments inhibited both classical alternative pathways The inhibition activation was reversible. Studies with overlapping peptides indicated functional activity located in cyclic 13-amino...
Decay-accelerating factor (DAF) is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that inhibits both the classical and alternative pathways of complement activation. DAF has been studied extensively in humans under two clinical settings: when absent from erythrocytes paroxysmal nocturnal hemoglobinuria (PNH) patients, who suffer complement-mediated hemolytic anemia, transgenic pigs expressing human DAF, which have developed to help overcome hyperacute rejection...
In all other species analyzed to date, the functionally active form of complement component C3 exists as product a single gene. We have now identified and characterized three functional proteins (C3-1, C3-3, C3-4) in trout that are products at least two distinct genes. All composed an alpha-and beta-chain contain thioester bond alpha-chain. However, they differ their electrophoretic mobility, glycosylation, reactivity with monospecific antibodies, relative ability bind various surfaces...
Abstract Vaccinia virus complement control protein (VCP) is a virulence determinant of vaccinia that helps protect the from attack host. To characterize interaction VCP with C3 and C4 understand mechanism by which inactivates complement, we have expressed in yeast expression system compared biologic activity purified to human factor H receptor 1 (CR1). Recombinant bound proteolytically cleaved form (C3b), but not 135,300-m.w. fragment generated using elastase (C3c) 35,000-m.w. (C3d)...
Background: Atypical hemolytic uremic syndrome (aHUS), an important cause of acute kidney injury (AKI), is characterized by dysregulation the alternative complement pathway. Autoantibodies to factor H (FH), a chief regulator this pathway, account for distinct subgroup. While high anti-FH titers predict relapse, they do not correlate well with disease activity and their functional characterization required. Methods: Of 781 patients <18-year-old aHUS in nationwide database from 2007 2018, 436...
Immune evasion is critical for survival of viruses that establish persistent or recurrent infections. However, at the molecular level, little known about how evade immune attack in vivo. Herpes simplex virus (HSV)-1 glycoprotein gC has two domains are involved modulating complement activation; one binds C3, and other required blocking C5 properdin (P) binding to C3. To evaluate importance these regions vivo, HSV-1 mutant were constructed lacked both studied a murine model infection. Each...
We have previously identified a 13-residue cyclic peptide, Compstatin, that binds to complement component C3 and inhibits activation. Herein, we describe the binding kinetics, structure-activity relationship, biotransformation of Compstatin. Biomolecular interaction analysis using surface-plasmon resonance showed Compstatin bound native its fragments C3b C3c, but not C3d. While was biphasic, C3c followed 1:1 Langmuir model; affinities for were 22- 74-fold lower, respectively, than C3....
The specificity of the thioester-containing site in three plasma proteins is regulated by elements their protein structures other than thioester bond itself. Human C4A and alpha 2-macroglobulin preferentially form amide linkages while human C3 primarily forms ester with hydroxyl groups. We have examined found evidence strong preferences for certain carbohydrates, indications selectivity specific positions on those carbohydrates a preference terminal sugars polysaccharides. A testable set...
Abstract The third component of complement, C3, plays a central role in activation the classical, alternative, and lectin pathways complement activation. Recently, we have identified 13‐residue cyclic peptide (named Compstatin) that specifically binds to C3 inhibits To investigate topology contribution each critical residue binding Compstatin now determined solution structure using 2D NMR techniques; also synthesized substitution analogues used these study structure‐function relationships...
Glycoprotein C (gC) of both herpes simplex virus type 1 (HSV-1) and HSV-2 interacts with complement C3b protects the from complement-mediated neutralization. To study mechanism by which gC modulates activation, we expressed gC-1 gC-2 in a baculovirus expression system. Baculovirus recombinants containing genes spanning entire sequence (gC-1-TMR) or only extracellular domain(s) gC-1, gC-2, deletion mutant lacking residues 33 through 123 were sf9 insect cells. Binding proteins to human C3...
Fiane AE, Mollnes TE, Videm V, Hovig T, Høgåsen K, Mellbye OJ, Spruce L, Moore WT, Sahu A, Lambris JD. Compstatin, a peptide inhibitor of C3, prolongs survival ex vivo perfused xenografts. Xenotransplantation 1999; 6: 000‐000 ©Munksgaard, Copenhagen newly described C3‐binding peptide, inhibits complement activation by blocking C3 convertase‐mediated cleavage C3. As the is an essential part rejection reaction, we evaluated ability Compstatin to delay or prevent hyperacute in xenograft model....
The pandemic influenza A(H1N1) 2009 virus caused significant morbidity and mortality worldwide thus necessitating the need to understand host factors that influence its control. Previously, complement system has been shown provide protection during seasonal infection, however, role of individual pathways is not yet clear. Here, we have dissected intact as well activation infection using mouse strains deficient in various components. We show C3-/- mice results increased viral load 100%...
Innate immunity in animals including humans encompasses the complement system, which is considered an important host defense mechanism against Aspergillus fumigatus, one of most ubiquitous opportunistic human fungal pathogens. Previously, it has been shown that alkaline protease Alp1p secreted from A. fumigatus mycelia degrades components C3, C4, and C5. However, remains unclear how spores (i.e. conidia) defend themselves activities system immediately after inhalation into lung. Here, we...
Abstract The molecular mechanisms involved in the interaction of complement receptor 2 (CR2) with its natural ligands iC3b and C3d are still not well understood. In addition, studies regarding binding site(s) on C3 as affinities fragments for CR2 have produced contradictory results. present study, we used surface plasmon resonance technology to study C3d, iC3b, EBV glycoprotein gp350/220. We measured kinetics ligands, examined influence ionic contacts these interactions, assessed whether...