ArticleJournal of immunology (Baltimore, Md. : 1950)2005
Electrostatic modeling predicts the activities of orthopoxvirus complement control proteins.
Article in Journal of immunology (Baltimore, Md. : 1950), 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 67 citations in OpenAlex.
- The grand escape - how pathogens outsmart the human complement system.Immunobiology · 2025Review
- Insight into mode-of-action and structural determinants of the compstatin family of clinical complement inhibitors.Nature communications · 2022Article
- Potential participation of CTRP6, a complement regulator, in the pathology of age related macular degeneration.Japanese journal of ophthalmology · 2022Article
- Complement component C3: A structural perspective and potential therapeutic implications.Seminars in immunology · 2022Review
- Incorporation of CD55 into the Zika Viral Envelope Contributes to Its Stability against Human Complement.Viruses · 2021Article
- Virus-Encoded Complement Regulators: Current Status.Viruses · 2021Review
- Role of Electrostatic Hotspots in the Selectivity of Complement Control Proteins Toward Human and Bovine Complement Inhibition.Frontiers in molecular biosciences · 2021Article
- Interference of the Zika Virus E-Protein With the Membrane Attack Complex of the Complement System.Frontiers in immunology · 2020Article
- Species Specificity of Vaccinia Virus Complement Control Protein for the Bovine Classical Pathway Is Governed Primarily by Direct Interaction of Its Acidic Residues with Factor I.Journal of virology · 2017Article
- Complement Evasion Strategies of Viruses: An Overview.Frontiers in microbiology · 2017Review
- Complement component C3 - The "Swiss Army Knife" of innate immunity and host defense.Immunological reviews · 2016Review
- Regulators of complement activity mediate inhibitory mechanisms through a common C3b-binding mode.The EMBO journal · 2016Article
- Anti-complement activity of the Ixodes scapularis salivary protein Salp20.Molecular immunology · 2016Article
- Article
- The vaccinia virus A56 protein: a multifunctional transmembrane glycoprotein that anchors two secreted viral proteins.The Journal of general virology · 2011Review
- Electrostatic clustering and free energy calculations provide a foundation for protein design and optimization.Annals of biomedical engineering · 2011Review
- The Vaccinia virus complement control protein modulates adaptive immune responses during infection.Journal of virology · 2011Article
- Influence of glycosylation and oligomerization of vaccinia virus complement control protein on level and pattern of functional activity and immunogenicity.Protein & cell · 2010Article
- Poxvirus complement control proteins are expressed on the cell surface through an intermolecular disulfide bridge with the viral A56 protein.Journal of virology · 2010Article
- Ectromelia virus inhibitor of complement enzymes protects intracellular mature virus and infected cells from mouse complement.Journal of virology · 2010Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Regulation of complement activation by pathogens and the host are critical for survival. Using two highly related orthopoxvirus proteins, the vaccinia and variola (smallpox) virus complement control proteins, which differ by only 11 aa, but differ 1000-fold in their ability to regulate complement activation, we investigated the role of electrostatic potential in predicting functional activity. Electrostatic modeling of the two proteins predicted that altering the vaccinia virus protein to contain the amino acids present in the second short consensus repeat domain of the smallpox protein would result in a vaccinia virus protein with increased complement regulatory activity. Mutagenesis of the vaccinia virus protein confirmed that changing the electrostatic potential of specific regions of the molecule influences its activity and identifies critical residues that result in enhanced function as measured by binding to C3b, inhibition of the alternative pathway of complement activation, and cofactor activity. In addition, we also demonstrate that despite the enhanced activity of the variola virus protein, its cofactor activity in the factor I-mediated degradation of C3b does not result in the cleavage of the alpha' chain of C3b between residues 954-955. Our data have important implications in our understanding of how regulators of complement activation interact with complement, the regulation of the innate immune system, and the rational design of potent complement inhibitors that might be used as therapeutic agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.