ArticleThe Journal of biological chemistry2014
Using mutagenesis and structural biology to map the binding site for the Plasmodium falciparum merozoite protein PfRh4 on the human immune adherence receptor.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Two noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections.Nature communications · 2024Article
- Complement receptor 1 is the human erythrocyte receptor forProceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Molecular Mechanisms of Complement Receptor 1-It Is Complicated.Biomolecules · 2023Review
- Structural biology of complement receptors.Frontiers in immunology · 2023Review
- The Cellular and Molecular Interaction Between Erythrocytes andFrontiers in cellular and infection microbiology · 2022Review
- Deregulation of Factor H by Factor H-Related Protein 1 Depends on Sialylation of Host Surfaces.Frontiers in immunology · 2021Article
- No Evidence that Knops Blood Group Polymorphisms Affect Complement Receptor 1 Clustering on Erythrocytes.Scientific reports · 2017Article
- Protection of host cells by complement regulators.Immunological reviews · 2016Review
- Identification of a reticulocyte-specific binding domain of Plasmodium vivax reticulocyte-binding protein 1 that is homologous to the PfRh4 erythrocyte-binding domain.Scientific reports · 2016Article
- Regulators of complement activity mediate inhibitory mechanisms through a common C3b-binding mode.The EMBO journal · 2016Article
- Red cell receptors as access points for malaria infection.Current opinion in hematology · 2016Review
- Red blood cell complement receptor one level varies with Knops blood group, α(+)thalassaemia and age among Kenyan children.Genes and immunity · 2016Article
- The Plasmodium falciparum blood stages acquire factor H family proteins to evade destruction by human complement.Cellular microbiology · 2016Article
- Characterization of Inhibitors and Monoclonal Antibodies That Modulate the Interaction between Plasmodium falciparum Adhesin PfRh4 with Its Erythrocyte Receptor Complement Receptor 1.The Journal of biological chemistry · 2015Article
- Role of complement receptor 1 (CR1; CD35) on epithelial cells: A model for understanding complement-mediated damage in the kidney.Molecular immunology · 2015Article
- Host-parasite interactions that guide red blood cell invasion by malaria parasites.Current opinion in hematology · 2015Review
- The apicomplexan glideosome and adhesins - Structures and function.Journal of structural biology · 2015Review
- Network-based gene prediction for Plasmodium falciparum malaria towards genetics-based drug discovery.BMC genomics · 2015Article
- Human gene copy number variation and infectious disease.Human genetics · 2014Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
To survive and replicate within the human host, malaria parasites must invade erythrocytes. Invasion can be mediated by the P. falciparum reticulocyte-binding homologue protein 4 (PfRh4) on the merozoite surface interacting with complement receptor type 1 (CR1, CD35) on the erythrocyte membrane. The PfRh4 attachment site lies within the three N-terminal complement control protein modules (CCPs 1-3) of CR1, which intriguingly also accommodate binding and regulatory sites for the key complement activation-specific proteolytic products, C3b and C4b. One of these regulatory activities is decay-accelerating activity. Although PfRh4 does not impact C3b/C4b binding, it does inhibit this convertase disassociating capability. Here, we have employed ELISA, co-immunoprecipitation, and surface plasmon resonance to demonstrate that CCP 1 contains all the critical residues for PfRh4 interaction. We fine mapped by homologous substitution mutagenesis the PfRh4-binding site on CCP 1 and visualized it with a solution structure of CCPs 1-3 derived by NMR and small angle x-ray scattering. We cross-validated these results by creating an artificial PfRh4-binding site through substitution of putative PfRh4-interacting residues from CCP 1 into their homologous positions within CCP 8; strikingly, this engineered binding site had an ∼30-fold higher affinity for PfRh4 than the native one in CCP 1. These experiments define a candidate site on CR1 by which P. falciparum merozoites gain access to human erythrocytes in a non-sialic acid-dependent pathway of merozoite invasion.
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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.