Abstract：
Regulation of membrane protein integration involves molecular devices such as Sec-translocons or the insertase YidC. We have identified an integration-promoting factor in the inner membrane of Escherichia coli called membrane protein integrase (MPIase). Structural analysis revealed that, despite its enzyme-like name, MPIase is a glycolipid with a long glycan comprising N-acetyl amino sugars, a pyrophosphate linker, and a diacylglycerol (DAG) anchor. Additionally, we found that DAG, a minor membrane component, blocks spontaneous integration. In this review, we demonstrate how they contribute to Sec-independent membrane protein integration in bacteria using a comprehensive approach including synthetic chemistry and biophysical analyses. DAG blocks unfavorable spontaneous integrations by suppressing mobility in the membrane core, whereas MPIase compensates for this. Moreover, MPIase plays critical roles in capturing a substrate protein to prevent its aggregation, attracting it to the membrane surface, facilitating its insertion into the membrane, and delivering it to other factors. The combination of DAG and MPIase efficiently regulates the integration of membrane proteins.
摘要：
膜蛋白整合的调节涉及分子装置，例如Sec-tranlocons或插入酶YidC。我们已经确定了大肠杆菌内膜中的整合促进因子，称为膜蛋白整合酶（MPIase）。结构分析表明，尽管它的名字像酶一样，MPIase是一种糖脂，具有包含N-乙酰氨基糖的长聚糖，焦磷酸盐接头，和二酰基甘油(DAG)锚。此外,我们发现DAG,一个次要的膜组件，阻断自发整合。在这次审查中,我们使用包括合成化学和生物物理分析在内的综合方法证明了它们如何有助于细菌中不依赖Sec的膜蛋白整合。DAG通过抑制膜核心的移动性来阻止不利的自发整合，而MPIase弥补了这一点。此外，MPIase在捕获底物蛋白以防止其聚集中起关键作用，将其吸引到膜表面，促进其插入膜中，并将其传递给其他因素。DAG和MPIase的组合有效地调节膜蛋白的整合。
