美国洛克菲勒大学Jue Chen研究小组发现，溶血素A的分泌系统是一个包含三个ABC转运体的多引擎泵。相关论文于2022年9月1日发表在《细胞》杂志上。

据研究人员介绍，1型分泌系统（T1SS）广泛存在于致病性革兰氏阴性细菌中，在合成整个多肽后挤出蛋白质底物。大肠杆菌溶血素A分泌系统一直被认为是T1SS结构和机制研究的原型。三个膜蛋白：内膜ABC转运体HlyB、适应蛋白HlyD和外膜孔蛋白TolC，是分泌所必需的。然而，该复合物的化学计量和结构尚不清楚。

研究人员发现，在两种构象中确定的冷冻电镜（cryo-EM）结构显示，内膜复合物是由三个HlyB同源二聚体和六个HlyD亚单位组成的异源十二元组。功能研究表明，HlyB和HlyD的低聚体化对蛋白质的分泌至关重要，多肽通过HlyB的典型ABC转运途径进行转运。这些数据表明，T1SS包含三个ABC转运体，一个作为蛋白通道，两个为转运过程提供异构动力。

附：英文原文

Title: The hemolysin A secretion system is a multi-engine pump containing three ABC transporters

Author: Hongtu Zhao, James Lee, Jue Chen

Issue&Volume: 2022/09/01

Abstract: Type 1 secretion systems (T1SSs) are widespread in pathogenic Gram-negative bacteria, extruding protein substrates following synthesis of the entire polypeptide. The Escherichia coli hemolysin A secretion system has long been considered a prototype in structural and mechanistic studies of T1SSs. Three membrane proteins—an inner membrane ABC transporter HlyB, an adaptor protein HlyD, and an outer membrane porin TolC—are required for secretion. However, the stoichiometry and structure of the complex are unknown. Here, cryo-electron microscopy (cryo-EM) structures determined in two conformations reveal that the inner membrane complex is a hetero-dodecameric assembly comprising three HlyB homodimers and six HlyD subunits. Functional studies indicate that oligomerization of HlyB and HlyD is essential for protein secretion and that polypeptides translocate through a canonical ABC transporter pathway in HlyB. Our data suggest that T1SSs entail three ABC transporters, one that functions as a protein channel and two that allosterically power the translocation process.

DOI: 10.1016/j.cell.2022.07.017

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00920-5