CEITEC - Central European Institute of Technology, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic.
National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
J Phys Chem Lett. 2024 Jan 11;15(1):175-179. doi: 10.1021/acs.jpclett.3c02785. Epub 2023 Dec 28.
Curvature sensing is an essential ability of biomolecules to preferentially localize to membrane regions of a specific curvature. It has been shown that amphipathic helices (AHs), helical peptides with both hydrophilic and hydrophobic regions, could sense a positive membrane curvature. The origin of this AH sensing has been attributed to their ability to exploit lipid-packing defects that are enhanced in regions of positive curvature. In this study, we revisit an alternative framework where AHs act as sensors of local internal stress within the membrane, suggesting the possibility of an AH sensing a negative membrane curvature. Using molecular dynamics simulations, we gradually tuned the hydrophobicity of AHs, thereby adjusting their insertion depth so that the curvature preference of AHs is switched from positive to negative. This study suggests that highly hydrophobic AHs could preferentially localize proteins to regions of a negative membrane curvature.
曲率感应是生物分子的一种基本能力，使其能够优先定位到具有特定曲率的膜区域。已经表明，两亲性螺旋（AHs），即具有亲水和疏水区域的螺旋肽，能够感应正曲率的膜。这种 AH 感应的起源归因于它们利用脂质堆积缺陷的能力，这些缺陷在正曲率区域得到增强。在这项研究中，我们重新审视了另一种框架，即 AHs 作为膜内局部内应力的传感器，这表明 AH 有可能感应到负曲率的膜。使用分子动力学模拟，我们逐渐调整 AHs 的疏水性，从而调整它们的插入深度，使得 AHs 的曲率偏好从正变为负。这项研究表明，高度疏水性的 AHs 可以优先将蛋白质定位到具有负曲率的膜区域。
