Uncovering the biophysical mechanism of Receptor for Advanced Glycation Endproducts molecular function

揭示高级糖基化终产物受体分子功能的生物物理机制

• 批准号: 1412084
• 负责人: Emily Smith
• 金额: $ 42万
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1412084&HistoricalAwards=false
• 关键词: Uncovering; biophysical; mechanism; Receptor; Advanced

Proteins in the cell membrane play a role in integrating the cell with its surrounding environment. For example, the receptor for advanced glycation endproducts (called RAGE) has many functions including a role in immunity. An important aspect of membrane protein function is the ability to move throughout the entire cell membrane to interact with other biological components, and characterizing this movement is critical to understanding how these proteins function. This project provides missing information to advance the understanding of how other biological components affect RAGE movement in the cell membrane. The award also enables the training of graduate, undergraduate and high school students. Partners in these endeavors include two programs: one pre-college program aimed to increase the number of ethnically diverse Iowa students who pursue science degrees and the other aimed to helps Iowans understand biotechnology developments. The Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Emily A. Smith from Iowa State University to characterize the effects of chemically-defined ligand binding events, cytoplasmic interactions, and other membrane components on RAGE diffusion and clustering using fluorescence microscopy combined with live cell measurements. The primary microscopy techniques to be used include single particle tracking, fluorescence resonance energy transfer and fluorescence recovery after photobleaching. Details of the molecular mechanism of a pattern-recognition receptor including the effects of ligand affinity, valency, and chemical composition on RAGE clustering and diffusion will be elucidated for the first time. This project provides missing information to advance the understanding of an important receptor associated with innate immunity and numerous pathophysiological conditions.

细胞膜中的蛋白质在将细胞与周围环境集成在一起方面发挥了作用。 例如，晚期糖基化最终产物的受体（称为RAGE）具有许多功能，包括在免疫中作用。膜蛋白功能的一个重要方面是能够在整个细胞膜中移动以与其他生物学成分相互作用，而表征这种运动对于理解这些蛋白质的功能至关重要。该项目提供了缺失的信息，以促进对其他生物成分如何影响细胞膜愤怒运动的理解。该奖项还可以培训研究生，本科和高中生。这些努力的合作伙伴包括两个计划：一个预科课程，旨在增加攻读科学学位的爱荷华州学生的数量，另一个旨在帮助爱荷华州理解生物技术发展。化学分部的生命过程计划计划是为爱荷华州立大学的Emily A. Smith博士提供资金，以表征化学定义的配体结合事件，细胞质相互作用以及其他膜成分对使用荧光显微镜组合的愤怒扩散和聚类的影响进行活细胞测量。要使用的主要显微镜技术包括单个粒子跟踪，荧光共振能量转移和光漂白后的荧光恢复。模式识别受体的分子机制的细节，包括配体亲和力，价值和化学成分对愤怒聚类和扩散的影响。该项目提供了缺失的信息，以促进对与先天免疫和众多病理生理状况相关的重要受体的理解。

项目成果

Lateral diffusion and signaling of receptor for advanced glycation end-products (RAGE): a receptor involved in chronic inflammation

晚期糖基化终产物受体 (RAGE) 的横向扩散和信号传导：一种参与慢性炎症的受体

• DOI: 10.1007/s00249-017-1227-5
• 发表时间: 2018
• 期刊: European Biophysics Journal
• 作者: Syed, Aleem;Zhu, Qiaochu;Smith, Emily A.
• 通讯作者: Smith, Emily A.

BODIPY-Derived Photoremovable Protecting Groups Unmasked with Green Light

• DOI: 10.1021/jacs.5b01297
• 发表时间: 2015-03-25
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Goswami, Pratik P.;Syed, Aleem;Winter, Arthur H.
• 通讯作者: Winter, Arthur H.

Ligand binding affinity and changes in the lateral diffusion of receptor for advanced glycation endproducts (RAGE)

配体结合亲和力和晚期糖基化终产物受体横向扩散的变化 (RAGE)

• DOI: 10.1016/j.bbamem.2016.10.001
• 发表时间: 2016
• 期刊: Biochimica et Biophysica Acta (BBA
• 作者: Syed, Aleem;Zhu, Qiaochu;Smith, Emily A.
• 通讯作者: Smith, Emily A.

Raman Imaging in Cell Membranes, Lipid-Rich Organelles, and Lipid Bilayers

• DOI: 10.1146/annurev-anchem-061516-045317
• 发表时间: 2017-01-01
• 期刊: ANNUAL REVIEW OF ANALYTICAL CHEMISTRY, VOL 10
• 作者: Syed, Aleem;Smith, Emily A.
• 通讯作者: Smith, Emily A.