CHP1与NHE1的C端两亲性螺旋HC1结合,并在NHE1的内向和外向构象之间呈现不同的结合角度。小分子药物Cariporide与底物钠离子竞争性结合在NHE1靠近胞外侧的底物结合口袋中,并且阻滞了结构域间的相对运动,从而抑制了NHE1-CHP1复合物的转运活性。 中国科学院生物物理所赵岩研究员、张凯研究员和加拿大McGill University的Jo...
Here, we elucidate structures of the human NHE1-CHP1 complex in both inward- and inhibitor (cariporide)-bound outward-facing conformations. We find that NHE1 assembles as a symmetrical homodimer, with each subunit undergoing an elevator-like conformational change during cation exchange. The cryo...
To investigate how the NHE1-CHP1 complex is activated by protonation, we prepared a sample at pH 6.5 as well as in the presence of 150-mM NaCl. Three-dimensional reconstruction of the corresponding NHE1-CHP1Na/6.5dataset was similar to the NHE1-CHP1Na/7.5dataset, resulting in a 3.4-...
CHP1 is ubiquitously expressed and its interaction with NHE promotes basal activity. While CHP2 expression is limited to the gut in non-diseased tissue, it is highly expressed in lung and other tumor cells. When CHP2 or NHE1 expression is diminished, tumor cell growth is nearly abrogated. ...
该研究报道了人源NHE3-CHP1内向开口构象的复合物结构,揭示了NHE3自抑制调控机制、磷脂酰肌醇分子(PI)增强NHE3转运活性的分子机理,以及CHP1对NHE3活性的调控机制。 2021年,本团队首次报道了NHE1-CHP1复合物内向构象和结合Cariporide的外向构象的高分辨率结构,系统地揭示了NHE1在底物转运过程中的构象变化,并且阐明...
该研究报道了人源NHE3-CHP1内向开口构象的复合物结构,揭示了NHE3自抑制调控机制、磷脂酰肌醇分子(PI)增强NHE3转运活性的分子机理,以及CHP1对NHE3活性的调控机制。 2021年,该团队首次报道了NHE1-CHP1复合物内向构象和结合Cariporide的外向构象的高分辨率结构,系统揭示了NHE1在底物转运过程中的构象变化,并阐明了NHE...
CHP3 as well as both regions of NHE1 in question were produced and purified. CHP3 specifically formed stable complexes with the CHP-binding region (CBD) of NHE1 (residues 503–545) in size-exclusion chromatography (SEC), but not with the C-terminal region (CTD, residues 633–815). CTD...
该研究报道了人源NHE3-CHP1内向开口构象的复合物结构,揭示了NHE3自抑制调控机制、磷脂酰肌醇分子(PI)增强NHE3转运活性的分子机理,以及CHP1对NHE3活性的调控机制[强]研究利用冷冻电镜单颗粒技术,解析了人源NHE3-CHP1复合物内向开口构象的高分辨率结构。在总体结构上,人源NHE3与NHE1结构类似,均呈现同源二聚体形式...
Effect of CHP1 expression on the ezrin-mediated control of NHE3 activity.Victor BabichFrancesca Di Sole
NHE3的功能障碍与肾脏和消化系统疾病有关。在这里,我们报告了人类NHE3-CHP1复合物向内构象的低温电子显微镜结构。我们发现NHE3中的一个胞质螺旋-环-螺旋基序阻断了核心和二聚结构域之间形成的胞内空腔,起到自抑制作用,并阻碍底物的转运。此外,发现两个磷脂酰肌醇分子结合在复合物的膜旁,起到锚定作用稳定复合物的...