High-pressure macromolecular crystallography as a tool for studying protein flexibility
Abstract
Protein function depends on their conformational flexibility. Complementary to temperature-dependent studies, high-pressure (HP) macromolecular crystallography is well suited to exploring the conformational space of proteins at atomic resolution. We have developed a new HP cell concept for macromolecular X-ray crystallography that overcomes the limitations of current devices. It consists of a single-crystalline sapphire capillary, which is loaded with multiple crystals and pressurized with helium at freely adjustable gas pressures of up to 120 MPa. Studying five different proteins, we generally observed a compression of the protein structures and a decrease in thermal displacement parameters at high pressure. Structurally, observations included the compression of a central tunnel of a biotechnologically relevant enzyme and the stabilization of ligand binding in the membrane protein photosynthetic reaction center of Cereibacter sphaeroides . For two pharmaceutically relevant proteins, the human kinase DRAK2 and SARS-CoV-2 main protease, we identified concerted movements of subdomains. Such knowledge is essential for predictions of protein dynamics and defined conformational states, offering the potential for improved structure-based drug development.
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BibTeX
@article{lieske2026highpressure,
title = {{High-pressure macromolecular crystallography as a tool for studying protein flexibility}},
author = {Julia Lieske and Sofiane Saouane and Patrick Y. A. Reinke and Sven Falke and Wiebke Ewert and Jan Meyer and Tim Pakendorf and Anja Burkhardt and Eva Crosas and Johanna Hakanpää and Karolina Stachnik and Jochen Sieg and Matthias Rarey and Miriam Aßmann and Henning Zaun and Jürgen Kuballa and Georgii K. Selikhanov and Azat G. Gabdulkhakov and Henry N. Chapman and Sebastian Günther and Alke Meents},
journal = {IUCrJ},
year = {2026},
month = oct,
doi = {10.1107/s2052252526008468},
url = {https://journals.iucr.org/paper?S2052252526008468},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - High-pressure macromolecular crystallography as a tool for studying protein flexibility
AU - Julia Lieske
AU - Sofiane Saouane
AU - Patrick Y. A. Reinke
AU - Sven Falke
AU - Wiebke Ewert
AU - Jan Meyer
AU - Tim Pakendorf
AU - Anja Burkhardt
AU - Eva Crosas
AU - Johanna Hakanpää
AU - Karolina Stachnik
AU - Jochen Sieg
AU - Matthias Rarey
AU - Miriam Aßmann
AU - Henning Zaun
AU - Jürgen Kuballa
AU - Georgii K. Selikhanov
AU - Azat G. Gabdulkhakov
AU - Henry N. Chapman
AU - Sebastian Günther
AU - Alke Meents
PY - 2026
DA - 2026/10/19
JO - IUCrJ
DO - 10.1107/s2052252526008468
UR - https://journals.iucr.org/paper?S2052252526008468
AB - Protein function depends on their conformational flexibility. Complementary to temperature-dependent studies, high-pressure (HP) macromolecular crystallography is well suited to exploring the conformational space of proteins at atomic resolution. We have developed a new HP cell concept for macromolecular X-ray crystallography that overcomes the limitations of current devices. It consists of a single-crystalline sapphire capillary, which is loaded with multiple crystals and pressurized with helium at freely adjustable gas pressures of up to 120 MPa. Studying five different proteins, we generally observed a compression of the protein structures and a decrease in thermal displacement parameters at high pressure. Structurally, observations included the compression of a central tunnel of a biotechnologically relevant enzyme and the stabilization of ligand binding in the membrane protein photosynthetic reaction center of Cereibacter sphaeroides . For two pharmaceutically relevant proteins, the human kinase DRAK2 and SARS-CoV-2 main protease, we identified concerted movements of subdomains. Such knowledge is essential for predictions of protein dynamics and defined conformational states, offering the potential for improved structure-based drug development.
SN - 2052-2525
ER -