Lack of Evidence from Studies of Soluble Protein Fragments that Knops Blood Group Polymorphisms in Complement Receptor-Type 1 Are Driven by Malaria
- Author(s)
- Tetteh-Quarcoo, PB; Schmidt, CQ; Tham, WH; Hauhart, R; Mertens, HDT; Rowe, A; Atkinson, JP; Cowman, AF; Rowe, JA; Barlow, PN;
- Details
- Publication Year 2012-04-10,Volume 7,Issue #4,Page e34820
- Journal Title
- PLOS ONE
- Publication Type
- Journal Article
- Abstract
- Complement receptor-type 1 (CR1, CD35) is the immune-adherence receptor, a complement regulator, and an erythroid receptor for Plasmodium falciparum during merozoite invasion and subsequent rosette formation involving parasitized and non-infected erythrocytes. The non-uniform geographical distribution of Knops blood group CR1 alleles Sl1/2 and McC(a/b) may result from selective pressures exerted by differential exposure to infectious hazards. Here, four variant short recombinant versions of CR1 were produced and analyzed, focusing on complement control protein modules (CCPs) 15-25 of its ectodomain. These eleven modules encompass a region (CCPs 15-17) key to rosetting, opsonin recognition and complement regulation, as well as the Knops blood group polymorphisms in CCPs 24-25. All four CR1 15-25 variants were monomeric and had similar axial ratios. Modules 21 and 22, despite their double-length inter-modular linker, did not lie side-by-side so as to stabilize a bent-back architecture that would facilitate cooperation between key functional modules and Knops blood group antigens. Indeed, the four CR1 15-25 variants had virtually indistinguishable affinities for immobilized complement fragments C3b (K-D = 0.8-1.1 mu M) and C4b (K-D = 5.0-5.3 mu M). They were all equally good co-factors for factor I-catalysed cleavage of C3b and C4b, and they bound equally within a narrow affinity range, to immobilized C1q. No differences between the variants were observed in assays for inhibition of erythrocyte invasion by P. falciparum or for rosette disruption. Neither differences in complement-regulatory functionality, nor interactions with P. falciparum proteins tested here, appear to have driven the non-uniform geographic distribution of these alleles.
- Publisher
- PUBLIC LIBRARY SCIENCE
- Keywords
- SMALL-ANGLE SCATTERING; PLASMODIUM-FALCIPARUM; HUMAN ERYTHROCYTES; INVASION PATHWAYS; C3B/C4B RECEPTOR; LIGAND-BINDING; ACTIVE-SITES; C3B BINDING; CCP MODULE; FACTOR-H
- Research Division(s)
- Infection And Immunity
- Publisher's Version
- https://doi.org/10.1371/journal.pone.0034820
- Open Access at Publisher's Site
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323580/- Terms of Use/Rights Notice
- Copyright: © 2012 Tetteh-Quarcoo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creation Date: 2012-04-10 12:00:00