日期：2026/9/1 (星期二)
時間：自15時30分至17時00分
主持人：鄭原忠教授
演講地點：臺大化學系積學館二樓潘貫講堂
演講者: Shou-Ting Hsieh Ph.D. candidate (謝守庭博士候選人)
演講者單位：Department of Chemistry, The University of Chicago
演講題目：Revealing structural origin of the cooperative membrane protein binding to phosphatidylserine (PS) lipids
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Date：2026/9/1 (Tue.)
Time：15:30-17:00
Host：Prof. Yuan-Chung Cheng (鄭原忠教授)
Location：Pan-Kuan Lecture Hall, 2nd floor of Dept. of Chemistry, NTU
Speaker：Shou-Ting Hsieh Ph.D. candidate
Affiliation: Department of Chemistry, The University of Chicago
Title：Revealing structural origin of the cooperative membrane protein binding to phosphatidylserine (PS) lipids
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Abstract:
Human transmembrane immunoglobulin and mucin domain protein 4 (hTIM4) is a phosphatidylserine (PS)-binding protein expressed on the membrane surface of many immune cells. hTIM4 utilizes its PS-binding pocket in the IgV domain, mediated by calcium ions, to recognize PS lipids in the target cells, such as apoptotic cells. However, the level of PS exposure in cells varies significantly depending on the cell status. The variation implies that various amount of PS exposure can be a factor to influence binding affinity of hTIM4. In this study, we aim to understand how membrane-binding of hTIM4 responds to the variation of PS exposure, and to identify key molecular contacts of membrane binding. hTIM4’s response to the variation of PS exposure was examined using a tryptophan fluorescence assay. Our data show that hTIM4 prefers to bind to vesicles with higher PS mole fractions. While there exists a single PS-binding pocket in hTIM4, the protein is found to bind to PS lipid in a cooperative manner.
To elucidate this observed cooperativity, we obtaineda representative bound structure of hTIM4 using X-ray reflectivity (XR) combined with molecular dynamics (MD) simulations. Our results indicate that the representative orientation from XR fitting is in good agreement with the orientational distribution from all-atom simulations. The bound structure reveals potentially favorable electrostatic interactions between four positively charged residues and negatively charged PS lipids in the vicinity of the binding pocket. Among them, Lys44 and Arg49 are found to be in frequenct contact to PS lipids. Our work is the first time to obtain the membrane-bound structure of a member of the human TIM protein family, revealing the cause for the cooperative binding nature in spite of the presernce of a single binding pocket. The combined methods of XR andMD simulations can be more generally used to yield the membrane-bound structure of a peripharal membrane protein.
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