Dynamical Behavior of the Human Ferroportin Homologue from Bdellovibrio bacteriovorus: Insight into the Ligand Recognition Mechanism.
Dynamical Behavior of the Human Ferroportin Homologue from Bdellovibrio bacteriovorus: Insight into the Ligand Recognition Mechanism.
复制标题
人类产弧菌铁转运蛋白同源物的动力学行为：对配体识别机制的洞察。
DOI：
10.3390/ijms21186785
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发表时间：
2020-09-16
影响因子：
5.6
通讯作者：
Polticelli F
中科院分区：
文献类型：
--
作者：
Tortosa V;Bonaccorsi di Patti MC;Iacovelli F;Pasquadibisceglie A;Falconi M;Musci G;Polticelli F
转运蛋白主要促进体超家族（MFS）的成员在许多生理过程中发挥重要作用，如发育、神经传递和信号传导。MFS蛋白的异常功能与多种疾病有关，包括癌症、精神分裂症、癫痫、肌萎缩侧索硬化症和阿尔茨海默病。MFS转运体也参与细菌和真菌的多药耐药。大多数MFS成员的结构，特别是那些具有显著生理相关性的成员的结构尚未得到解决。结构和功能信息的缺乏阻碍了我们对这些转运体的详细了解，从而阻碍了这些转运体的药理靶向。为了提高我们对控制MSF成员功能的机制原理的认识，对革兰氏阴性细菌Bdellovibrio bacteriovorus （BdFpn）的人类铁转运蛋白同源物的内向和外向晶体结构进行了分子动力学（MD）模拟。为了探索蛋白质动力学与配体识别机制之间的关系，还进行了一些过量铁离子的模拟。这些结果强化了已经为其他MFS成员描述的交替访问机制的存在。此外，盐桥的重组（其中一些在几个MFS成员中保守）似乎是促进转运体构象变化的关键分子事件。
Members of the major facilitator superfamily of transporters (MFS) play an essential role in many physiological processes such as development, neurotransmission, and signaling. Aberrant functions of MFS proteins are associated with several diseases, including cancer, schizophrenia, epilepsy, amyotrophic lateral sclerosis and Alzheimer’s disease. MFS transporters are also involved in multidrug resistance in bacteria and fungi. The structures of most MFS members, especially those of members with significant physiological relevance, are yet to be solved. The lack of structural and functional information impedes our detailed understanding, and thus the pharmacological targeting, of these transporters. To improve our knowledge on the mechanistic principles governing the function of MSF members, molecular dynamics (MD) simulations were performed on the inward-facing and outward-facing crystal structures of the human ferroportin homologue from the Gram-negative bacterium Bdellovibrio bacteriovorus (BdFpn). Several simulations with an excess of iron ions were also performed to explore the relationship between the protein’s dynamics and the ligand recognition mechanism. The results reinforce the existence of the alternating-access mechanism already described for other MFS members. In addition, the reorganization of salt bridges, some of which are conserved in several MFS members, appears to be a key molecular event facilitating the conformational change of the transporter.
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影响因子：
4.8
作者：
Adler, J;Bibi, E
通讯作者：
Bibi, E
影响因子：
16
作者：
Fluman N;Ryan CM;Whitelegge JP;Bibi E
通讯作者：
Bibi E
影响因子：
11.4
作者：
Edgar, R;Bibi, E
通讯作者：
Bibi, E
影响因子：
4.4
作者：
FELLER, SE;ZHANG, YH;BROOKS, BR
通讯作者：
BROOKS, BR
影响因子：
5.5
作者：
Li, Pengfei;Roberts, Benjamin P.;Chakravorty, Dhruva K.;Merz, Kenneth M., Jr.
通讯作者：
Merz, Kenneth M., Jr.