题 目：A cool tail of a warm Channel

主 讲：杜鹃 教授（美国西北大学）

时 间：2026年4月2日（周四）上午10:10-11:30

地 点：琳恩图书馆111报告厅

报告摘要：

Temperature profoundly affects macromolecular function, particularly in proteins with temperature sensitivity. However, its impact is often overlooked in biophysical studies typically performed at non-physiological temperatures, potentially leading to inaccurate mechanistic and pharmacological insights. This is demonstrated in our present study of TRPM4, a temperature-sensitive Ca2+-activated ion channel. By studying TRPM4 prepared at physiological temperature using single-particle cryo-electron microscopy, we discovered a “warm” conformation, distinct from those observed at lower temperatures. This conformation is driven by a temperature-dependent Ca2+ binding site in the intracellular domain, and is essential for TRPM4 function in physiological contexts. We demonstrated that ligands, exemplified by decavanadate (DVT, a positive modulator) and ATP (an inhibitor), bind to different locations at physiological temperature than at lower temperatures; and that these sites have bona fide functional relevance. We elucidated the TRPM4 gating mechanism by capturing structural snapshots of its different functional states at physiological temperature, revealing the elusive channel opening not observed at lower temperatures. Our work represents the first example of temperature-dependent ligand recognition and modulation of an ion channel, underscoring the importance of studying macromolecules at physiological temperature. It also provides a potential molecular framework for deciphering how thermosensitive TRPM channels perceive temperature changes.

嘉宾简介：

杜娟教授（Juan Du）现任美国西北大学教授。她的研究聚焦于感官感知的分子机制，特别是人体如何通过神经元离子通道检测温度、味道等外界刺激，并将这些信号传递至大脑以诱发相应反应。杜娟教授拥有深厚的生物化学与结构生物学背景，在德国弗莱堡大学获得化学博士学位，并在美国Vollum Institute完成博士后研究。

她领导的实验室致力于破解感觉神经科学领域的未解之谜，重点关注温度感知与味觉感知的生物物理机制。研究团队采用多学科交叉的研究方法，从分子层面阐明温度和味觉感知的基础原理，并探索其与疼痛及代谢疾病之间的关联。研究内容包括：在动物模型和分子水平探讨温度如何影响味觉感知，以及基于结构的药物设计，开发用于疼痛治疗和代谢疾病干预的新型策略。

杜娟教授曾荣获多项重要学术荣誉，包括Pew生物医学科学学者奖（Pew Scholar in the Biomedical Sciences）、斯隆神经科学研究奖（Sloan Research Fellowship in Neuroscience）、克林根斯坦-西蒙斯神经科学学者奖（Klingenstein-Simons Award in the Neuroscience）以及McKnight神经科学学者奖（McKnight Scholar Award for Neuroscience）等。