近日，美国哥伦比亚大学教授Chi-Min Ho及其团队的研究开发出了入侵疟原虫结合和重塑宿主膜的结构基础。相关论文于2026年6月30日发表在《细胞》杂志上。

该课题组研究人员确定了从侵袭停滞的恶性疟原虫中直接纯化的移动连接的基本重复单元的内源性结构，揭示了一个帆船形状的顶端膜抗原1（PfAMA1）和瘤颈蛋白2,4和5 （PfRON2， PfRON4和PfRON5）的1:1 1:1组装。课题组人员观察到两个PfRON2跨膜螺旋将复合物锚定在红细胞（RBC）膜上，并显示一个细胞外手柄用于PfAMA1结合。PfAMA1直接接触红细胞膜，加强了连接。PfRON2/4/5在红细胞内形成一个大的基本平台，通过静电作用与红细胞膜结合，并将7个两亲螺旋楔入双分子层，提示其在宿主膜重塑中起积极作用。然后，该团队利用其结构揭示的天然膜背景，以及计算蛋白质设计的最新进展，使合理设计抑制入侵的小蛋白质粘合剂成为可能。

据介绍，疟原虫移动接头是疟疾宿主细胞入侵的核心，但其功能尚不清楚。

附：英文原文

Title: Structural basis for host membrane binding and remodeling by invading malaria parasites

Author: Meseret T. Haile, Daphne A. Kaxiras, James Zhen, Carolyn L. Lee, Britney Jiang, Jennifer L. Small-Saunders, Chi-Min Ho

Issue&Volume: 2026-06-30

Abstract: The Plasmodium moving junction is central to malarial host-cell invasion, and yet its function remains unclear. Here, we determine the endogenous structure of the basic repeating unit of the moving junction, purified directly from invasion-stalled Plasmodium falciparum parasites, revealing a sailboat-shaped 1:1:1:1 assembly of apical membrane antigen 1 (PfAMA1) and rhoptry neck proteins 2, 4, and 5 (PfRON2, PfRON4, and PfRON5). We observe two PfRON2 transmembrane helices that anchor the complex in the red blood cell (RBC) membrane and display an extracellular handle for PfAMA1 binding. PfAMA1 directly contacts the RBC membrane, strengthening the connection. PfRON2/4/5 form a large, basic platform inside the RBC that electrostatically engages the RBC membrane and wedges seven amphipathic helices deep into the bilayer, suggesting an active role in host-membrane remodeling. We then leverage the native membrane context revealed by our structure, along with recent advances in computational protein design, to enable the rational design of a small protein binder that inhibits invasion.

DOI: 10.1016/j.cell.2026.06.012

Source: https://www.cell.com/cell/abstract/S0092-8674(26)00699-9

期刊信息

Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：66.85

官方网址：https://www.cell.com/

投稿链接：https://www.editorialmanager.com/cell/default.aspx