2MCY

CR1 Sushi domains 2 and 3

2MCY の概要

• エントリーDOI: 10.2210/pdb2mcy/pdb
• 関連するPDBエントリー: 2MCZ
• NMR情報: BMRB: 19458
• 分子名称: Complement receptor type 1 (1 entity in total)
• 機能のキーワード: cr1, pfrh4, malaria, ccp, immune system
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P17927
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14675.49

構造登録者

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. (登録日: 2013-08-27, 公開日: 2013-11-13, 最終更新日: 2014-01-22)

主引用文献

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

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: 24214979
DOI: 10.1074/jbc.M113.520346

実験手法

SOLUTION NMR