Powder Diffraction Methods for Membrane Protein Structure Determination

用于膜蛋白结构测定的粉末衍射方法

• 批准号: BB/J020702/1
• 负责人: Bonnie Wallace
• 金额: $ 14.95万
• 依托单位: Birkbeck, University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ020702%2F1
• 关键词: Powder; Diffraction; Methods; Membrane; Protein

Membrane proteins comprise a large proportion of all the proteins coded by human and other eukaryotic genomes, and are the targets of more than one-half of all the pharmaceutical drugs marketed today. Knowledge of their three-dimensional structure is important for understanding how they function, and for the development of new drugs for the treatment of diseases. Protein X-ray crystallographic studies, which require well-ordered, large single crystals of the protein, provide such structural information. However, one of the major obstacles to membrane protein structure determinations currently is the ability to produce crystals of a size and quality suitable for single crystal studies. Although often many much smaller crystals can be produced, there has yet to be a method developed to utilise these for the determination of the structure of membrane proteins. The aim of this project is to develop both the methodology and tools necessary to determine the structure of membrane proteins based on samples not of single crystals, but of bunches of very small (microcrystals) using powder diffraction techniques.

膜蛋白包括人类和其他真核基因组编码的所有蛋白质中的很大一部分，并且是当今销售的所有药物中一半以上的靶标。了解其三维结构对于理解它们的功能以及用于治疗疾病的新药物很重要。蛋白质X射线晶体学研究需要有序的大型蛋白质单晶，提供了这种结构信息。但是，当前确定膜蛋白结构的主要障碍之一是能够产生适合单晶研究的尺寸和质量的晶体。尽管通常可以产生许多较小的晶体，但尚未开发出一种方法来确定膜蛋白的结构。该项目的目的是开发基于不是单晶的样品，而是使用粉末衍射技术来确定膜蛋白结构所需的方法和工具。

项目成果

Role of the C-terminal domain in the structure and function of tetrameric sodium channels.

• DOI: 10.1038/ncomms3465
• 发表时间: 2013
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Bagneris, Claire;DeCaen, Paul G.;Hall, Benjamin A.;Naylor, Claire E.;Clapham, David E.;Kay, Christopher W. M.;Wallace, B. A.
• 通讯作者: Wallace, B. A.

Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing.

• DOI: 10.1038/ncomms2077
• 发表时间: 2012
• 期刊: Nature communications
• 影响因子: 16.6

Cannabidiol interactions with voltage-gated sodium channels.

• DOI: 10.7554/elife.58593
• 发表时间: 2020-10-22
• 期刊: eLife
• 影响因子: 7.7
• 作者: Sait LG;Sula A;Ghovanloo MR;Hollingworth D;Ruben PC;Wallace BA
• 通讯作者: Wallace BA

Sodium Ion Coordination in the Selectivity Filter of a Voltage-Gated Sodium Channel

电压门控钠通道选择性过滤器中的钠离子配位

• DOI: 10.1016/j.bpj.2014.11.2681
• 发表时间: 2015
• 期刊: Biophysical Journal
• 影响因子: 3.4
• 作者: Naylor C

Structural model of the open-closed-inactivated cycle of prokaryotic voltage-gated sodium channels.

• DOI: 10.1085/jgp.201411242
• 发表时间: 2015-01
• 期刊: The Journal of general physiology
• 作者: Bagnéris C;Naylor CE;McCusker EC;Wallace BA
• 通讯作者: Wallace BA