2026年9月10日，德国明斯特大学儿童医院Heymut Omran等科学家在《科学》（Science）发表研究，解析了人类纤毛过渡区的原位结构，并将连接复合物缺陷与原发性纤毛运动障碍联系起来。

纤毛过渡区（TZ）调控纤毛蛋白质组的组成，但其分子结构、蛋白质含量及其对运动性纤毛病的贡献仍不明确。研究人员将原位冷冻电子断层扫描和亚断层平均技术应用于人类多纤毛上皮细胞。该方法以亚纳米分辨率解析了TZ特异性二联体微管，并鉴定出九种组成蛋白。研究人员发现，ECT2L和DZANK1在相邻TZ二联体微管之间形成主要的连接复合物。任一基因的双等位功能丧失变异均会导致原发性纤毛运动障碍。ECT2L和DZANK1缺陷破坏了TZ结构，引起微管异常和异常的球状纤毛尖端，并损害黏液纤毛清除功能。这些发现确立了TZ缺陷与人类运动性纤毛病之间的直接遗传联系，并说明了原位结构生物学如何揭示人类疾病机制。

附：英文原文

Title: In situ structure of the human ciliary transition zone links linker defects to primary ciliary dyskinesia

Author: Haixia Zhou, Lea Terbeck, Andrew Berical, Marine Brunet, Sven M. Lange, Jacob R. Anderson, Heike Olbrich, Diana Carolin Bracht, Kai Wohlgemuth, Cynthia Rieck, Johanna Raidt, Jürgen Klingauf, Sivagurunathan Sutharsan, Huda Mussaffi, Dario Prais, Victoria Dunphy, Sachiko T. Homma, Paul Guichard, Virginie Hamel, Finn J. Hawkins, Heymut Omran, Alan Brown

Issue&Volume: 2026-09-10

Abstract: The ciliary transition zone (TZ) regulates ciliary proteome composition, yet its molecular architecture, protein content, and contribution to motile ciliopathies remain poorly defined. We applied in situ cryo-electron tomography and subtomogram averaging to human multiciliated epithelial cells. This approach resolved TZ-specific doublet microtubules at subnanometer resolution and identified nine constituent proteins. We identified that ECT2L and DZANK1 form the major linker complexes between adjacent TZ doublet microtubules. Biallelic loss-of-function variants in either gene cause primary ciliary dyskinesia. ECT2L and DZANK1 deficiency disrupted TZ architecture, caused microtubular abnormalities and abnormal bulbous ciliary tips, and impaired mucociliary clearance. These findings establish a direct genetic link between TZ defects and human motile ciliopathy, and illustrate how in situ structural biology can uncover mechanisms of human disease.

DOI: 10.1126/science.aei595

Source: https://www.science.org/doi/10.1126/science.aei5957