Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
Department of Chemistry, University of Wisconsin, Madison, WI, 53706, USA.
Angew Chem Int Ed Engl. 2017 Feb 6;56(7):1756-1759. doi: 10.1002/anie.201609708. Epub 2017 Jan 10.
Small-residue-mediated interhelical packings are ubiquitously found in helical membrane proteins, although their interaction dynamics and lipid dependence remain mostly uncharacterized. We used a single-pair FRET technique to examine the effect of a GXXXG motif on the association of de novo designed (AALALAA) helices in liposomes. Dimerization occurred with sub-second lifetimes, which was abolished by cholesterol. Utilizing the nearly instantaneous time-resolution of 2D IR spectroscopy, parallel and antiparallel helix associations were identified by vibrational couplings across helices at their interface. Taken together, the data illustrate that the GXXXG motif controls helix packing but still allows for a dynamic and lipid-regulated oligomeric state.
小残基介导的螺旋间堆积普遍存在于螺旋膜蛋白中，尽管其相互作用动力学和脂质依赖性在很大程度上仍未得到阐明。我们使用单对 FRET 技术研究了 GXXXG 基序对脂质体中从头设计的（AALALAA）螺旋体缔合的影响。二聚化发生在亚秒级的寿命内，胆固醇会使其失活。利用二维红外光谱的近瞬时时间分辨率，通过在其界面处跨螺旋的振动耦合，鉴定了平行和反平行的螺旋体缔合。总之，这些数据表明，GXXXG 基序控制着螺旋堆积，但仍允许形成动态的和受脂质调节的寡聚状态。
