Department of Physics, School of Physics and Electronic Science, East China Normal University, 500 Dongchuan Road, Minhang District, Shanghai 200241, China.
Department of Biochemistry, University of Oxford, South Park Road, Oxford OX1 3QU, UK.
Int J Mol Sci. 2022 Jun 21;23(13):6913. doi: 10.3390/ijms23136913.
S-TGA-1 and PGP-Me are native archaeal lipids associated with the bacteriorhodopsin (bR) trimer and contribute to protein stabilization and native dynamics for proton transfer. However, little is known about the underlying molecular mechanism of how these lipids regulate bR trimerization and efficient photocycling. Here, we explored the specific binding of S-TGA-1 and PGP-Me with the bR trimer and elucidated how specific interactions modulate the bR trimeric structure and proton release and uptake using long-term atomistic molecular dynamic simulations. Our results showed that S-TGA-1 and PGP-Me are essential for stabilizing the bR trimer and maintaining the coherent conformational dynamics necessary for proton transfer. The specific binding of S-TGA-1 with W80 and K129 regulates proton release on the extracellular surface by forming a "Glu-shared" model. The interaction of PGP-Me with K40 ensures proton uptake by accommodating the conformation of the helices to recruit enough water molecules on the cytoplasmic side. The present study results could fill in the theoretical gaps of studies on the functional role of archaeal lipids and could provide a reference for other membrane proteins containing similar archaeal lipids.
S-TGA-1 和 PGP-Me 是与菌紫质（bR）三聚体相关的天然古菌脂质，有助于蛋白质稳定和质子转移的天然动力学。然而，对于这些脂质如何调节 bR 三聚体形成和高效光循环的潜在分子机制知之甚少。在这里，我们探索了 S-TGA-1 和 PGP-Me 与 bR 三聚体的特异性结合，并通过长期原子分子动力学模拟阐明了特定相互作用如何调节 bR 三聚体结构和质子释放和摄取。我们的结果表明，S-TGA-1 和 PGP-Me 对于稳定 bR 三聚体和维持质子转移所需的相干构象动力学是必不可少的。S-TGA-1 与 W80 和 K129 的特异性结合通过形成“Glu 共享”模型调节细胞外表面的质子释放。PGP-Me 与 K40 的相互作用通过容纳螺旋的构象来确保质子摄取，从而在细胞质侧募集足够的水分子。本研究结果可以填补古菌脂质功能作用研究的理论空白，并为其他含有类似古菌脂质的膜蛋白提供参考。
