Molecular dynamics simulations of wild type and mutants of human complement receptor 2 complexed with C3d

• Published in: Physical chemistry chemical physics : PCCP Vol. 15; no. 4; pp. 1241 - 1251
• Main Authors: Wan, Hua, Hu, Jian-ping, Tian, Xu-hong, Chang, Shan
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 28.01.2013
• Subjects: Adaptive systems; Chemistry; Complement; Complement C3d - chemistry; Complement C3d - genetics; Complement C3d - metabolism; Exact sciences and technology; General and physical chemistry; Human; Humans; Molecular dynamics; Molecular Dynamics Simulation; Molecular structure; Mutagenesis; Principal Component Analysis; Protein Binding; Protein Structure, Tertiary; Receptors; Receptors, Complement 3d - chemistry; Receptors, Complement 3d - genetics; Receptors, Complement 3d - metabolism; Simulation; Thermodynamics; Human; Molecular dynamics; Complement receptor type 2; Simulation
• ISSN: 1463-9076; 1463-9084
• DOI: 10.1039/c2cp41388d

The interaction between human complement receptor type 2 (CR2) and antigen-bound C3d can bridge the innate and adaptive immune systems. The recently determined structure of the CR2(SCR1-2):C3d complex has revealed the expected binding interface of CR2-C3d. In this article, wild type (WT) and three mutants of the new structure are studied by molecular dynamics (MD) simulations. The differently decreased structural stabilities of the mutants relative to WT are shown to be consistent with the experimental data, which can be explained by the different hydrogen bond patterns at the interfaces. It is also found that two clusters of residues (D36/E37/E39 and E160/D163/E166) in the acidic pocket of C3d are important for CR2-C3d interactions, which is in good agreement with previous mutagenesis study. In addition, functional dynamics and the conformational change of CR2 are explored by using domain cross-correlation map (DCCM), principal component analysis (PCA), and free energy landscape (FEL) methods. The conformational change mainly corresponds to the opening of a V-shaped structure of CR2, which is consistent with the previously reported high interdomain flexibility of CR2. We further suppose that the opening of a V-shaped structure of CR2 may favor the binding stability of CR2(SCR1-2):C3d. This study would provide some new insights into the understanding of the CR2-C3d interaction mechanism. Molecular dynamics studies suggest that a more open V-shaped conformation of CR2(SCR1-2) favors the binding stability of CR2(SCR1-2):C3d complex.