Kuang Guanglin, Liang Lijun, Brown Christian, Wang Qi, Bulone Vincent, Tu Yaoquan
Division of Theoretical Chemistry and Biology, School of Biotechnology, Royal Institute of Technology (KTH), AlbaNova University Center, 106 91 Stockholm, Sweden.
Division of Glycoscience, School of Biotechnology, Royal Institute of Technology (KTH), AlbaNova University Center, 106 91 Stockholm, Sweden.
Phys Chem Chem Phys. 2016 Feb 21;18(7):5281-90. doi: 10.1039/c5cp05391a.
The critical role of chitin synthases in oomycete hyphal tip growth has been established. A microtubule interacting and trafficking (MIT) domain was discovered in the chitin synthases of the oomycete model organism, Saprolegnia monoica. MIT domains have been identified in diverse proteins and may play a role in intracellular trafficking. The structure of the Saprolegnia monoica chitin synthase 1 (SmChs1) MIT domain has been recently determined by our group. However, although our in vitro assay identified increased strength in interactions between the MIT domain and phosphatidic acid (PA) relative to other phospholipids including phosphatidylcholine (PC), the mechanism used by the MIT domain remains unknown. In this work, the adsorption behavior of the SmChs1 MIT domain on POPA and POPC membranes was systematically investigated by molecular dynamics simulations. Our results indicate that the MIT domain can adsorb onto the tested membranes in varying orientations. Interestingly, due to the specific interactions between MIT residues and lipid molecules, the binding affinity to the POPA membrane is much higher than that to the POPC membrane. A binding hotspot, which is critical for the adsorption of the MIT domain onto the POPA membrane, was also identified. The lower binding affinity to the POPC membrane can be attributed to the self-saturated membrane surface, which is unfavorable for hydrogen-bond and electrostatic interactions. The present study provides insight into the adsorption profile of SmChs1 and additionally has the potential to improve our understanding of other proteins containing MIT domains.
几丁质合成酶在卵菌菌丝尖端生长中的关键作用已得到证实。在卵菌模式生物——单核腐霉的几丁质合成酶中发现了一个微管相互作用与运输（MIT）结构域。MIT结构域已在多种蛋白质中被鉴定出来，可能在细胞内运输中发挥作用。我们团队最近确定了单核腐霉几丁质合成酶1（SmChs1）的MIT结构域的结构。然而，尽管我们的体外试验表明，相对于包括磷脂酰胆碱（PC）在内的其他磷脂，MIT结构域与磷脂酸（PA）之间的相互作用强度有所增加，但其作用机制仍不清楚。在这项工作中，通过分子动力学模拟系统地研究了SmChs1的MIT结构域在POPA和POPC膜上的吸附行为。我们的结果表明，MIT结构域可以以不同的方向吸附到测试膜上。有趣的是，由于MIT残基与脂质分子之间的特定相互作用，其对POPA膜的结合亲和力远高于对POPC膜的结合亲和力。还确定了一个对MIT结构域吸附到POPA膜至关重要的结合热点。对POPC膜较低的结合亲和力可归因于自饱和的膜表面，这不利于氢键和静电相互作用。本研究深入了解了SmChs1的吸附情况，还有助于增进我们对其他含有MIT结构域的蛋白质的理解。
