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The molecular mechanism of pH‐regulating C3d‐CR2 interactions: Insights from molecular dynamics simulation
Author(s) -
Zhang Yan,
Guo Jingjing,
Ning Lulu,
Tian Jiaqi,
Yao Xiaojun,
Liu Huanxiang
Publication year - 2019
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13460
Subject(s) - protonation , chemistry , molecular dynamics , hydrogen bond , molecular model , linker , molecule , biophysics , stereochemistry , computational chemistry , organic chemistry , biology , ion , computer science , operating system
Abstract The interactions of complement receptor 2 (CR2) and the degradation fragment C3d of complement component C3 mediate the innate and adaptive immune systems. Due to the importance of C3d‐CR2 interaction in the design of vaccines, many studies have indicated the interactions are pH‐dependent. Moreover, C3d‐CR2 interactions at pH 5.0 are unknown. To investigate the molecular mechanism of pH‐regulating C3d‐CR2 interaction, molecular dynamics simulations for C3d‐CR2 complex in different pH are performed. Our results revealed that the protonation of His9 in C3d at pH 6.0 slightly weakens C3d‐CR2 association as reducing pH from 7.4 to 6.0, initiated from a key hydrogen bond formed between Gly270 and His9 in C3d at pH 6.0. When reducing pH from 6.0 to 5.0, the protonation of His33 in C3d weakens C3d‐SCR1 association by changing the hydrogen‐bond network of Asp36, Glu37, and Glu39 in C3d with Arg13 in CR2. In addition, the protonation of His90 significantly enhances C3d‐SCR2 association. This is because the enhanced hydrogen‐bond interactions of His90 with Glu63 and Ser69 of the linker change the conformations of the linker, Cys112‐Asn116 and Pro87‐Gly91 regions. This study uncovers the molecular mechanism of the mediation of pH on C3d‐CR2 interaction, which is valuable for vaccine design.