Gai Wei, Wang Yuhang, Martin Brianna, Zhang Junjie, Carr Chavela M, Rye Hays S
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77845, USA.
Sci Adv. 2025 Aug;11(31):eads9443. doi: 10.1126/sciadv.ads9443. Epub 2025 Aug 1.
Membrane-enclosed transport carriers return biological molecules from the recycling endosome to the plasma membrane using a mechanism that is not well understood. In , the formation of carriers from the recycling endosome requires the amphiphysin protein AMPH-1. Recently, we found that purified AMPH-1 is sufficient for tubulation and vesiculation of liposomes in a mechanism that is regulated by guanine nucleotides. Here, we propose a model linking guanosine 5'-triphosphate (GTP) binding and hydrolysis to the membrane binding and tubulation required for transport carrier formation. We find that GTP binding stabilizes interactions between AMPH-1 and the membrane through amphipathic, amino-terminal α helices, which are found at the tips of the arc-shaped, homodimeric structure. By contrast, in the posthydrolysis, guanosine diphosphate-bound state, these helices are repositioned to interact with the amino-terminal helices of other homodimers, to form an oligomeric AMPH-1 lattice that tubulates the membrane, in preparation for carrier formation by membrane fission.
膜封闭运输载体利用一种尚未完全了解的机制将生物分子从回收型内体运回质膜。在[具体情况未提及]中，从回收型内体形成载体需要发动蛋白AMPH-1。最近，我们发现纯化的AMPH-1足以通过一种受鸟嘌呤核苷酸调节的机制使脂质体形成微管和囊泡。在此，我们提出一个模型，将鸟苷5'-三磷酸（GTP）结合与水解与运输载体形成所需的膜结合和微管形成联系起来。我们发现GTP结合通过位于弧形同二聚体结构末端的两亲性氨基末端α螺旋稳定了AMPH-1与膜之间的相互作用。相比之下，在水解后鸟苷二磷酸结合状态下，这些螺旋重新定位以与其他同二聚体的氨基末端螺旋相互作用，形成一个使膜微管化的AMPH-1寡聚晶格，为通过膜裂变形成载体做准备。
