Lv Jian-Min, Huang Xiao-Ping, Chen Jun-Yao, Cheng Bin, Chen Wen-Zhuo, Yuan Ping, Wu Feng, Li Hai-Yun
MOE Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, PR China.
MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, PR China.
Mol Immunol. 2022 Dec;152:123-128. doi: 10.1016/j.molimm.2022.10.010. Epub 2022 Nov 2.
Human, rat, and mouse C-reactive protein (CRP) possess distinct expression patterns, but have similar conformations and conserved in vivo functions. We have previously demonstrated that this level-function mismatch is delicately tuned by the hidden activities of unfolded CRP. The cholesterol-binding sequence (CBS; a.a. 35-47) is a major functional motif exposed on monomeric CRP, which is the unfolded and activated conformation of CRP. We replaced the CBS of rat CRP with that of either mouse or human CRP, yielding two grafting mutants with unaffected pentameric assembly. However, these mutants exhibited altered cellular foldability and conformational activation efficiency that matched those of the CRP that provided the grafted CBS. These results indicate that CBS is a critical regulatory motif, whose variation maintains the pentameric assembly of CRP but derives distinct cellular foldabilities and conformational activation efficiencies, therefore helping to ensure that CRPs with various expression patterns exhibit overall conserved functions.
人、大鼠和小鼠的C反应蛋白（CRP）具有不同的表达模式，但具有相似的构象和保守的体内功能。我们之前已经证明，这种水平-功能不匹配是由未折叠的CRP的隐藏活性精细调节的。胆固醇结合序列（CBS；氨基酸35-47）是单体CRP上暴露的主要功能基序，单体CRP是CRP的未折叠和活化构象。我们用小鼠或人的CRP的CBS替换大鼠CRP的CBS，产生了两个五聚体组装不受影响的嫁接突变体。然而，这些突变体表现出改变的细胞折叠性和构象活化效率，与提供嫁接CBS的CRP的折叠性和效率相匹配。这些结果表明，CBS是一个关键的调节基序，其变异维持了CRP的五聚体组装，但产生了不同的细胞折叠性和构象活化效率，因此有助于确保具有各种表达模式的CRP表现出整体保守的功能。
