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混合与挤出：用于时间分辨蛋白质晶体学的高粘度样品注入

Mix-and-extrude: high-viscosity sample injection towards time-resolved protein crystallography.

作者信息

Vakili Mohammad, Han Huijong, Schmidt Christina, Wrona Agnieszka, Kloos Marco, de Diego Iñaki, Dörner Katerina, Geng Tian, Kim Chan, Koua Faisal H M, Melo Diogo V M, Rappas Mathieu, Round Adam, Round Ekaterina, Sikorski Marcin, Valerio Joana, Zhou Tiankun, Lorenzen Kristina, Schulz Joachim

机构信息

European XFEL GmbH, Holzkoppel 4, Schenefeld 22869, Germany.

Sosei Heptares, Steinmetz Building, Granta Park, Great Abington, Cambridge CB21 6DG, United Kingdom.

出版信息

J Appl Crystallogr. 2023 Jun 12;56(Pt 4):1038-1045. doi: 10.1107/S1600576723004405. eCollection 2023 Aug 1.

DOI:10.1107/S1600576723004405
PMID:37555221
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10405586/
Abstract

Time-resolved crystallography enables the visualization of protein molecular motion during a reaction. Although light is often used to initiate reactions in time-resolved crystallography, only a small number of proteins can be activated by light. However, many biological reactions can be triggered by the interaction between proteins and ligands. The sample delivery method presented here uses a mix-and-extrude approach based on 3D-printed microchannels in conjunction with a micronozzle. The diffusive mixing enables the study of the dynamics of samples in viscous media. The device design allows mixing of the ligands and protein crystals in 2 to 20 s. The device characterization using a model system (fluorescence quenching of iq-mEmerald proteins by copper ions) demonstrated that ligand and protein crystals, each within lipidic cubic phase, can be mixed efficiently. The potential of this approach for time-resolved membrane protein crystallography to support the development of new drugs is discussed.

摘要

时间分辨晶体学能够可视化反应过程中蛋白质的分子运动。尽管在时间分辨晶体学中常使用光来引发反应，但只有少数蛋白质能被光激活。然而，许多生物反应可由蛋白质与配体之间的相互作用触发。此处介绍的样品输送方法采用基于3D打印微通道并结合微喷嘴的混合挤出方法。扩散混合能够研究粘性介质中样品的动力学。该装置设计允许在2至20秒内混合配体和蛋白质晶体。使用模型系统（铜离子对iq-绿色荧光蛋白的荧光猝灭）进行的装置表征表明，脂质立方相中的配体和蛋白质晶体能够有效混合。本文还讨论了这种方法在时间分辨膜蛋白晶体学中支持新药开发的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/781e/10405586/0b9b604efa7d/j-56-01038-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/781e/10405586/2620617a72d1/j-56-01038-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/781e/10405586/21142b686d55/j-56-01038-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/781e/10405586/bada57aeb2ac/j-56-01038-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/781e/10405586/3d3e4eb8a06e/j-56-01038-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/781e/10405586/0b9b604efa7d/j-56-01038-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/781e/10405586/2620617a72d1/j-56-01038-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/781e/10405586/21142b686d55/j-56-01038-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/781e/10405586/bada57aeb2ac/j-56-01038-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/781e/10405586/3d3e4eb8a06e/j-56-01038-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/781e/10405586/0b9b604efa7d/j-56-01038-fig5.jpg

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