北京大学定量生物学中心

学术报告

题目: De novo design of functional transmembrane proteins

报告人: 卢培龙 特聘研究员

西湖大学生命科学学院

时间: 12月5日（周五）13:00-14:00

地点: 吕志和楼B101

主持人: 林一瀚教授、汪阳明教授

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.

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，从事计算生物学与生物物理学多学科交叉研究。近年来，精确设计了多种具有新型结构与功能的蛋白质，以通讯作者或第一作者身份在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。