Application of the SMALP system to generate antibodies for intact transmembrane proteins

应用 SMALP 系统生成完整跨膜蛋白抗体

• 批准号: BB/J010812/1
• 负责人: Michael Overduin
• 金额: $ 19.31万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ010812%2F1
• 关键词: Application; SMALP; system; generate; antibodies

The analysis and exploitation of transmembrane proteins has recently become one of the most exciting areas of drug discovery and biological research. About a third of all proteins are found in membranes, their mechanisms are particularly difficult to study as they are often present only in small amounts and are difficult to handle. These proteins are stabilized by their interactions with native lipids but current methods to study them depend on detergents which strip these lipids away. We have developed a novel bionanoparticle to prepare functionally intact proteins directly from native membrane maintaining the local lipid environment and propose to develop antibodies to these targets for therapeutic and research purposes. This new generation of antibodies will allow specific recognition of native protein states with unprecedented accuracy, and will enable development of new diagnostic tests and biotherapeutic agents for treatment of cancer and many infectious and genetic diseases.

跨膜蛋白的分析和开发最近已成为药物发现和生物学研究中最令人兴奋的领域之一。大约三分之一的蛋白质存在于膜中，其机制特别难以研究，因为它们通常仅少量存在且难以处理。这些蛋白质通过与天然脂质的相互作用而稳定，但目前研究它们的方法依赖于去除这些脂质的去污剂。我们开发了一种新型生物纳米颗粒，可以直接从维持局部脂质环境的天然膜制备功能完整的蛋白质，并建议开发针对这些靶标的抗体用于治疗和研究目的。新一代抗体将能够以前所未有的准确度特异性识别天然蛋白质状态，并将有助于开发新的诊断测试和生物治疗药物，用于治疗癌症和许多传染性和遗传性疾病。

项目成果

MODA, HADDOCK, and SMALP: new developments for unravelling membrane protein structure and function: Honorary Lecture

MODA、HADDOCK 和 SMALP：揭示膜蛋白结构和功能的新进展：荣誉讲座

• 发表时间: 2014
• 期刊: BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE
• 作者: Overduin Michael

NMR of Membrane Proteins: Beyond Crystals.

膜蛋白的核磁共振：超越晶体。

• DOI: 10.1007/978-3-319-35072-1_3
• 发表时间: 2016
• 期刊: Advances in experimental medicine and biology
• 作者: Rajesh S

Membrane biology visualized in nanometer-sized discs formed by styrene maleic acid polymers.

• DOI: 10.1016/j.bbamem.2017.10.019
• 发表时间: 2018-03
• 期刊: Biochimica et biophysica acta. Biomembranes
• 作者: Esmaili M;Overduin M
• 通讯作者: Overduin M

G-protein coupled receptor solubilization and purification for biophysical analysis and functional studies, in the total absence of detergent.

• DOI: 10.1042/bsr20140171
• 发表时间: 2015-04-16
• 期刊: Bioscience reports
• 影响因子: 4
• 作者: Jamshad M;Charlton J;Lin YP;Routledge SJ;Bawa Z;Knowles TJ;Overduin M;Dekker N;Dafforn TR;Bill RM;Poyner DR;Wheatley M
• 通讯作者: Wheatley M

Encapsulated membrane proteins: A simplified system for molecular simulation.

• DOI: 10.1016/j.bbamem.2016.02.039
• 发表时间: 2016-03
• 期刊: Biochimica et biophysica acta
• 作者: Sarah C. Lee;S. Khalid;N. Pollock;Timothy J. Knowles;K. Edler;A. Rothnie;Owen R T Thomas;T. Dafforn