title: The solvent at antigen-binding site regulated C3d-CR2 interactions through the C-terminal tail of C3d at different ion strengths: insights from molecular dynamics simulation.
abstract: The interactions of complement receptor 2 (CR2) and the degradation fragment C3d of complement component C3 play important links between the innate and adaptive immune systems. Due to the importance of C3d-CR2 interaction in the design of vaccines and inhibitors, a number of studies have been performed to investigate C3d-CR2 interaction. Many studies have indicated C3d-CR2 interactions are ionic strength-dependent.
  
  
  
  To investigate the molecular mechanism of C3d-CR2 interaction and the origin of effects of ionic strength, molecular dynamics simulations for C3d-CR2 complex together with the energetic and structural analysis were performed.
  
  
  
  Our results revealed the increased interactions between charged protein and ions weaken C3d-CR2 association, as ionic strengths increase. Moreover, ion strengths have similar effects on antigen-binding site and CR2 binding site. Meanwhile, Ala17 and Gln20 will transform between the activated and non-activated states mediated by His133 and Glu135 at different ion strengths.
  
  
  
  Our results reveal the origins of the effects of ionic strengths on C3d-CR2 interactions are due to the changes of water, ion occupancies and distributions.
  
  
  
  This study uncovers the origin of the effect of ionic strength on C3d-CR2 interaction and deepens the understanding of the molecular mechanism of their interaction, which is valuable for the design of vaccines and small molecule inhibitors.
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China; State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China; State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000, PR China. Electronic address: hxliu@lzu.edu.cn.
authors.forename: Huanxiang
authors.initials: H
authors.lastname: Liu
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000941:Antigens / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites / Q000276:immunology; D003176:Complement C3 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007477:Ions / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D009994:Osmolar Concentration; D011485:Protein Binding; D011487:Protein Conformation; D017464:Receptors, Complement 3d / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D014612:Vaccines / Q000737:chemistry / Q000276:immunology
chemical_list: D000941:Antigens; D003176:Complement C3; D007477:Ions; D046912:Multiprotein Complexes; D017464:Receptors, Complement 3d; D014612:Vaccines
keywords: C3d; CR2; Complement; MM-GBSA; Molecular dynamics simulation