Department of Cell Biology, New York University School of Medicine, New York, United States.
Applied Bioinformatics Laboratory, New York University School of Medicine, New York, United States.
Elife. 2020 Jun 30;9:e60030. doi: 10.7554/eLife.60030.
ABC transporters facilitate the movement of diverse molecules across cellular membranes, but how their activity is regulated post-translationally is not well understood. Here we report the crystal structure of MlaFB from , the cytoplasmic portion of the larger MlaFEDB ABC transporter complex, which drives phospholipid trafficking across the bacterial envelope to maintain outer membrane integrity. MlaB, a STAS domain protein, binds the ABC nucleotide binding domain, MlaF, and is required for its stability. Our structure also implicates a unique C-terminal tail of MlaF in self-dimerization. Both the C-terminal tail of MlaF and the interaction with MlaB are required for the proper assembly of the MlaFEDB complex and its function in cells. This work leads to a new model for how an important bacterial lipid transporter may be regulated by small proteins, and raises the possibility that similar regulatory mechanisms may exist more broadly across the ABC transporter family.
ABC 转运蛋白促进多种分子在细胞膜间的运动，但它们的翻译后活性如何调节还不是很清楚。我们报告了来自 的 MlaFB 的晶体结构，MlaFEDB ABC 转运体复合物的细胞质部分，它驱动磷脂在细菌包膜中的运输以维持外膜完整性。MlaB 是一种 STAS 结构域蛋白，与 ABC 核苷酸结合域 MlaF 结合，并稳定其结构。我们的结构还暗示 MlaF 的独特 C 末端尾部参与自身二聚化。MlaF 的 C 末端尾部和与 MlaB 的相互作用对于 MlaFEDB 复合物的正确组装及其在细胞中的功能都是必需的。这项工作为一种重要的细菌脂质转运蛋白如何可能受到小蛋白的调节提供了一个新的模型，并提出了类似的调节机制可能在 ABC 转运蛋白家族中更为普遍的可能性。
