报告题目：De novo design of functional transmembrane proteins for signal sensing and response
报告人：卢培龙  研究员
主持人：冯新华  教授
时   间：2026年1月15日（周四）下午4点
地   点：纳米楼457报告厅 
报告人简介：

卢培龙，西湖大学生命科学学院特聘研究员，新基石研究员。主要研究方向为蛋白质设计，进行计算生物学与生物物理学多学科交叉研究。精确设计了多种具有新型结构与功能的蛋白质。近年来，在Cell, Nature，Science, Cell Research, Nature Structural & Molecular Biology等期刊发表多篇论文。主持国家重点研发计划和国自然青年科学基金A类等项目。

讲座摘要：

Transmembrane proteins facilitate the exchange of materials, energy, and information across the cell membrane, thereby enabling cells to adapt more effectively to the surrounding environment. There has been de novo designed transmembrane proteins; however, they lack the ability to respond to specific environmental cues—such as voltage, pH, ligands, mechanical force, light, and temperature. Here, we report the de novo design of voltage-gated anion channels (VGAC) and transmembrane fluorescence-activating proteins (tmFAP). VGACs adopt a 15-helix pentameric structure featuring a constriction composed of five arginine residues within the transmembrane span. In patch-clamp experiments, VGACs displayed strictly voltage-dependent currents and demonstrated selectivity for chloride anions over iodide anions. Our data suggest that the arginine constriction undergoes voltage-induced conformational changes, serving as both the voltage sensor and selectivity filter. tmFAPs possess pre-organized ligand-binding pockets in high-quality 4-helix backbones for a fluorogenic ligand, and specifically activate the fluorescence of the target fluorophore with mid-nanomolar affinity, exhibiting higher brightness and quantum yield compared to EGFP. VGACs and tmFAPs function effectively in mammalian cells upon expression. Cryo-EM and crystal structures of the designed transmembrane proteins show a high degree of agreement with our design models. Collectively, our results provide novel insights into membrane biology and open avenues for a diverse array of applications.