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通过DNP增强的固态NMR光谱解决人类ABC载体TAP上的抗原识别

Elisa Lehnert, Jiafei Mao, Ahmad Reza Mehdipour¹

¹Department of Theoretical Biophysics, Max Planck Institute of Biophysics , Max-von-Laue-Str. 3, 60438 Frankfurt am Main, Germany.

Journal of the American Chemical Society

|September 24, 2016

概括

研究人员使用先进的NMR确定了与抗原结合的人类载体 (TAP) 的原子结构. 这揭示了TAP如何选择免疫反应和人类健康的.

科学领域:

生物化学
结构生物学
免疫学

背景情况:

与抗原处理相关的转运体 (TAP) 是参与适应性免疫的重要ABC转运体复合体.
了解-TAP相互作用是阐明对转化细胞的免疫反应的关键.
之前的研究缺乏关于与TAP结合的原子分辨率数据.

研究的目的:

确定与人体TAP结合的抗原的原子分辨率结构.
通过TAP获得选择和转位的机制见解.
为了确定TAP复合体内的结腔.

主要方法:

开发一种温和的方法来缩不稳定的膜蛋白复合物.
应用动态核极化增强的魔力角度旋转固态NMR光谱.
将NMR数据与分子建模集成.

主要成果:

在人体TAP中确定抗原的原子分辨率骨干构造.
对和TAP之间侧链相互作用的前所未有的洞察力.
通过联合NMR和建模识别结腔.

结论:

揭示了TAP的基材选择规则的结构和化学基础.
提供了人体免疫中-TAP识别的机制理解.
证明了固态核磁共振对真核转运蛋白的研究能力.

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ABC Transporters: Exporter

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ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...