Membrane Protein Crystallisation: Current Trends and Future Perspectives

Parker, Joanne L.; Newstead, Simon

doi:10.1007/978-3-319-35072-1_5

Cited by 43 publications

(41 citation statements)

References 42 publications

(54 reference statements)

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“…(a) Surfactants used to determine MP crystal structures. 37 (b) Surfactants used to determine structures of MPs from electron microscopy. (c) Surfactants used for solution-state NMR structures.…”

Section: Membrane Protein Structure In Native and Artificial Environmmentioning

confidence: 99%

Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies

et al. 2018

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Membrane proteins perform a host of vital cellular functions. Deciphering the molecular mechanisms whereby they fulfill these functions requires detailed biophysical and structural investigations. Detergents have proven pivotal to extract the protein from its native surroundings. Yet, they provide a milieu that departs significantly from that of the biological membrane, to the extent that the structure, the dynamics, and the interactions of membrane proteins in detergents may considerably vary, as compared to the native environment. Understanding the impact of detergents on membrane proteins is, therefore, crucial to assess the biological relevance of results obtained in detergents. Here, we review the strengths and weaknesses of alkyl phosphocholines (or foscholines), the most widely used detergent in solution-NMR studies of membrane proteins. While this class of detergents is often successful for membrane protein solubilization, a growing list of examples points to destabilizing and denaturing properties, in particular for α-helical membrane proteins. Our comprehensive analysis stresses the importance of stringent controls when working with this class of detergents and when analyzing the structure and dynamics of membrane proteins in alkyl phosphocholine detergents.

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Section: Membrane Protein Structure In Native and Artificial Environmmentioning

confidence: 99%

Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies

et al. 2018

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“…As a pivotal lipid among numerous synthetic glycolipids, octyl β-D-glucoside (β-OGlu) has long attracted attention owing to its versatile biochemical applications. Particularly intriguing features are that the compound mimics membrane lipids, binding with protein molecules via hydrogen bonding or hydrophobic interactions, and it co-crystallizes with protein molecules [1][2][3][4][5][6][7][8][9]. In addition, it is intrinsically self-assembling, a characteristic that emerges from the various phase behaviors that depend upon the concentration and temperature.…”

Section: Introductionmentioning

confidence: 99%

Unveiling the Uniqueness of Crystal Structure and Crystalline Phase Behavior of Anhydrous Octyl β-D-Glucoside Using Aligned Assembly on a Surface

Ogawa

Takahashi

2020

Polymers

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Although the anomalous low crystallinity of octyl β-D-glucoside (β-OGlu) was first proposed more than 30 years ago, many fundamental aspects of its crystal structure and of the crystalline phase behavior of the pure substance have remained uncertain. In this paper, we employ grazing-incidence wide-angle X-ray-diffraction measurements using a two-dimensional detector (2D-GI-WAXD) and perpendicularly aligned crystalline films to demonstrate that β-OGlu forms crystal structures consisting of an intermediate phase-like a ripple phase with two large crystal-lattice constants, a and c, comparable to the lengths of its bilayer structures. Furthermore, solid-to-solid phase transitions accompanied by latent heat confirm the existence of a solid-solution-like phase consisting of a crystalline and a liquid-crystal (LC) phase, which persists over a 20 • C temperature range, in a single-component system. In addition, the system forms a superlattice, accompanied by a change in packing of the component sugars in the partial-melting state; this shift is different from the gel-crystal transition observed for a typical lipid system. These facts indicate that even in the crystalline phase formed from a single component, each individual β-OGlu molecule in a single-component phase plays a versatile role in the crystallisation and melting processes. These findings must somewhat explain the specific co-assembling features with proteins of β-OGlu, which has long been used empirically in biochemistry.

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“…So far (updated on January 2019), the number of the available crystal structures for membrane proteins in Protein Data Bank (PDB) did not exceed ~3,5% of all deposited entries. Such a small fraction of resolved membrane proteins is primarily caused by problems when overexpressing membrane proteins in bacteria [ 101 ], as well as by the obstacles accompanying crystallization of membrane proteins [ 89 ]. These include, for example, finding optimal conditions for crystallization [ 87 ], as well as difficulties to account for a membrane-like environment which in turn is being crucial for crystallizing the native form of membrane proteins.…”

Section: Molecular Modeling Approaches At a Glancementioning

confidence: 99%

Current Advances in Studying Clinically Relevant Transporters of the Solute Carrier (SLC) Family by Connecting Computational Modeling and Data Science

Türková

Zdrazil

2019

Computational and Structural Biotechnology Journal

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Organic anion and cation transporting proteins (OATs, OATPs, and OCTs), as well as the Multidrug and Toxin Extrusion (MATE) transporters of the Solute Carrier (SLC) family are playing a pivotal role in the discovery and development of new drugs due to their involvement in drug disposition, drug-drug interactions, adverse drug effects and related toxicity. Computational methods to understand and predict clinically relevant transporter interactions can provide useful guidance at early stages in drug discovery and design, especially if they include contemporary data science approaches. In this review, we summarize the current state-of-the-art of computational approaches for exploring ligand interactions and selectivity for these drug (uptake) transporters. The computational methods discussed here by highlighting interesting examples from the current literature are ranging from semiautomatic data mining and integration, to ligand-based methods (such as quantitative structure-activity relationships, and combinatorial pharmacophore modeling), and finally structure-based methods (such as comparative modeling, molecular docking, and molecular dynamics simulations). We are focusing on promising computational techniques such as fold-recognition methods, proteochemometric modeling or techniques for enhanced sampling of protein conformations used in the context of these ADMET-relevant SLC transporters with a special focus on methods useful for studying ligand selectivity.

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Membrane Protein Crystallisation: Current Trends and Future Perspectives

Cited by 43 publications

References 42 publications

Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies

Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies

Unveiling the Uniqueness of Crystal Structure and Crystalline Phase Behavior of Anhydrous Octyl β-D-Glucoside Using Aligned Assembly on a Surface

Current Advances in Studying Clinically Relevant Transporters of the Solute Carrier (SLC) Family by Connecting Computational Modeling and Data Science

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