核苷酸诱导的构象运动与细菌 ABC 转运蛋白的跨门控动力学

ATP 结合盒 (ABC) 转运蛋白是整合膜蛋白，介导由 ATP 水解供能的多种底物跨膜交换。我们报告了对细菌血红素转运蛋白 HmuUV 进行的粗粒度动力学模拟结果。基于无核苷酸结构，我们构建了该蛋白的配体弹性网络描述，并在结构解析的计算机实验中研究了 ATP 诱导的构象运动。我们发现，与核苷酸的相互作用产生了功能性且稳健的通用运动。 Upon binding of ATP-mimicking ligands, the structure changed from a conformation in which the nucleotide-binding domains formed an open shape, to a conformation in which they were found in tight contact and the transmembrane domains were rotated. ( Upon binding of ATP-mimicking ligands, the structure changed from a conformation in which the nucleotide-binding domains formed an open shape, to a conformation in which they were found in tight contact and the transmembrane domains were rotated.) 结合模拟 ATP 的配体后，结构从核苷酸结合域呈开放形状的构象转变为两者紧密接触且跨膜域发生旋转的构象。在配体结合复合物中，血红素通道变宽，而在无核苷酸构象中关闭的通往细胞质的门控，通过涉及关键跨膜螺旋倾斜运动的机制被打开。基于我们的发现，我们提出 HmuUV 转运蛋白表现得像一个“简单”的机械装置，其中由 ATP 配体结合诱导的核苷酸结合域的线性运动转化为跨膜域的旋转运动和内部倾斜动力学，从而控制血红素通路内的门控。