据研究人员介绍，纤毛内运输（IFT）是一个高度保守的过程，通过IFT-A和IFT-B复合物的列车状聚合体，然后蛋白质沿着纤毛微管运输。IFT-A夹在IFT-B和纤毛膜之间，这与它在运输跨膜和膜相关货物方面的作用一致。
研究人员使用单粒子分析电子冷冻显微镜（cryo-EM）来确定了原生IFT-A复合物的结构。结果表明，亚复合物的重排使IFT-A能够在前向的IFT列车上横向聚合，这揭示了一种合作组装机制。令人惊讶的是，研究人员发现IFT-A与IFT-B的结合将首选的脂质结合界面从纤毛膜上屏蔽开来，但将一个具有容纳不同货物能力的β-推进器结构域的互联网络导向纤毛膜。这项工作为理解IFT-列车的组装和货物的相互作用提供了一个机制基础。
附：英文原文
Title: Mechanism of IFT-A polymerization into trains for ciliary transport
Author: Shimi Meleppattu, Haixia Zhou, Jin Dai, Miao Gui, Alan Brown
Issue&Volume: 2022/12/22
Abstract: Intraflagellar transport (IFT) is the highly conserved process by which proteins are transported along ciliary microtubules by a train-like polymeric assembly of IFT-A and IFT-B complexes. IFT-A is sandwiched between IFT-B and the ciliary membrane, consistent with its putative role in transporting transmembrane and membrane-associated cargoes. Here, we have used single-particle analysis electron cryomicroscopy (cryo-EM) to determine structures of native IFT-A complexes. We show that subcomplex rearrangements enable IFT-A to polymerize laterally on anterograde IFT trains, revealing a cooperative assembly mechanism. Surprisingly, we discover that binding of IFT-A to IFT-B shields the preferred lipid-binding interface from the ciliary membrane but orients an interconnected network of β-propeller domains with the capacity to accommodate diverse cargoes toward the ciliary membrane. This work provides a mechanistic basis for understanding IFT-train assembly and cargo interactions.
DOI: 10.1016/j.cell.2022.11.033
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01508-2