生命科学学院知识库

蛋白质与配体之间的分子识别及构象变化是阐明其生物功能的重要基础。研究发现关联心血管疾病与炎症的C-反应蛋白（C-reactive protein, CRP）的生物活性主要源于变构形式mCRP，其中促炎活性更是仅在五聚体结构解聚为单体后展现。mCRP显示出更强生物活性的机制及与多种模式配体相互识别的位点目前尚不明确。前期实验我们发现了一个胆固醇结合基序aa35-47，能够调控mCRP与多种配体的结合，同时该基序显示出的内源无序结构特性可能是胆固醇结合基序宽可塑性识别的分子基础。经过进一步的序列和功能分析，我们发现不同物种的蛋白中的胆固醇结合基序确实有类似的氨基酸序列特征且具备内源无序的结构倾向，表明其可能具有通用机制。基于前期调研，开展以mCRP为出发点的胆固醇结合基序宽可塑性的配体识别机制研究，将为以相关炎症疾病为标靶的早期治疗和干预策略提供理论依据。

Molecular recognition and conformational changes between proteins and ligands are important bases for elucidating their biological functions. It was found that the biological activity of C-reactive protein (CRP) associated with cardiovascular disease and inflammation was mainly due to the variant form of mCRP, in which the proinflammatory activity was only after the pentamer structure was depolymerized into monomer Show. The mechanism by which mCRP shows a stronger biological activity and a site that is identified with multiple mode ligands is not yet known. In the previous experiment, we found a cholesterol-binding motif aa35-47 that regulates the binding of mCRP to a variety of ligands while the motif shows that the endogenous disorder structure may be a molecular basis for the identification of cholesterol-binding motifs The After further sequence and functional analysis, we found that the cholesterol-binding motifs in the proteins of different species do have similar amino acid sequence characteristics and have endogenous disordered structural tendencies, suggesting that they may have a general mechanism. Based on the preliminary investigation, the study of ligand identification mechanism of cholesterol-binding motifs with mCRP as the starting point will provide the theoretical basis for early treatment and intervention strategies with related inflammatory diseases as the target.