2MCY
CR1 Sushi domains 2 and 3
Summary for 2MCY
Entry DOI | 10.2210/pdb2mcy/pdb |
Related | 2MCZ |
NMR Information | BMRB: 19458 |
Descriptor | Complement receptor type 1 (1 entity in total) |
Functional Keywords | cr1, pfrh4, malaria, ccp, immune system |
Biological source | Homo sapiens (human) |
Cellular location | Membrane; Single-pass type I membrane protein: P17927 |
Total number of polymer chains | 1 |
Total formula weight | 14675.49 |
Authors | Park, H.J.,Guariento, M.J.,Maciejewski, M.,Hauart, R.,Tham, W.,Cowman, A.F.,Schmidt, C.Q.,Martens, H.,Liszewski, K.M.,Hourcade, D.,Barlow, P.N.,Atkinson, J.P. (deposition date: 2013-08-27, release date: 2013-11-13, Last modification date: 2014-01-22) |
Primary citation | Park, H.J.,Guariento, M.,Maciejewski, M.,Hauhart, R.,Tham, W.H.,Cowman, A.F.,Schmidt, C.Q.,Mertens, H.D.,Liszewski, M.K.,Hourcade, D.E.,Barlow, P.N.,Atkinson, J.P. Using Mutagenesis and Structural Biology to Map the Binding Site for the Plasmodium falciparum Merozoite Protein PfRh4 on the Human Immune Adherence Receptor. J.Biol.Chem., 289:450-463, 2014 Cited by PubMed 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. PubMed: 24214979DOI: 10.1074/jbc.M113.520346 PDB entries with the same primary citation |
Experimental method | SOLUTION NMR |
Structure validation
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