Human galectin-7 (Gal-7; also termed p53-induced gene 1 product) is a multifunctional effector by productive pairing with distinct glycoconjugates and protein counter-receptors in the cytoplasm and nucleus, as well as on the cell surface. Its structural analysis by NMR spectroscopy detected doubling of a set of particular resonances, an indicator of Gal-7 existing in two conformational states in slow exchange on the chemical shift time scale. Structural positioning of this set of amino acids around the P4 residue and loss of this phenomenon in the bioactive P4L mutant indicated cis–trans isomerization at this site. Respective resonance assignments confirmed our proposal of two Gal-7 conformers. Mapping hydrogen bonds and considering van der Waals interactions in molecular dynamics simulations revealed a structural difference for the N-terminal peptide, with the trans-state being more exposed to solvent and more mobile than the cis-state. Affinity for lactose or glycan-inhibitable neuroblastoma cell surface contact formation was not affected, because both conformers associated with an overall increase in order parameters (S2). At low µM concentrations, homodimer dissociation is more favored for the cis-state of the protein than its trans-state. These findings give direction to mapping binding sites for protein counter-receptors of Gal-7, such as Bcl-2, JNK1, p53 or Smad3, and to run functional assays at low concentration to test the hypothesis that this isomerization process provides a (patho)physiologically important molecular switch for Gal-7.

中文翻译：

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人半乳凝素7中的Pro4脯氨酰肽键异构化调节单体-二聚体平衡以影响功能。

人半乳糖凝集素7（Gal-7；也称为p53诱导的基因1产物）是一种多功能效应器，通过在细胞质和细胞核以及细胞表面与独特的糖缀合物和蛋白质抗受体进行生产性配对。其通过NMR光谱的结构分析检测到一组特定共振的加倍，这是在化学位移时间尺度上以缓慢交换的两种构象状态存在的Gal-7指示剂。这组氨基酸在P4残基周围的结构定位以及这种现象在生物活性P4L突变体中的丢失表明该位点是顺反异构体。各自的共振分配证实了我们关于两个Gal-7构象异构体的提议。映射氢键并在分子动力学模拟中考虑范德华相互作用，揭示了N端肽的结构差异，与顺式相比，反式更易暴露于溶剂中，并且更具流动性。乳糖或聚糖抑制性神经母细胞瘤细胞表面接触形成的亲和力没有受到影响，因为这两个构象子均与顺序参数的总体增加相关（S2）。在低µM浓度下，同型二聚体解离比顺式更适合蛋白质的顺式状态。这些发现为定位Gal-7蛋白反受体（例如Bcl-2，JNK1，p53或Smad3）的结合位点提供了方向，