Article
Biochemical Research Methods
Jeffrey A. Julien, Sarah G. Mutchek, Martin G. Fernandez, Kerney Jebrell Glover
Summary: The study presents a simplified method for producing tagless MSP, utilizing expression as inclusion bodies followed by cleavage with cyanogen bromide, and purification by gel filtration chromatography. The produced MSP is capable of producing nanodiscs and lacks tryptophan residues, making it suitable for spectroscopic studies.
ANALYTICAL BIOCHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Stephen G. Sligar, Ilia G. Denisov
Summary: Membrane proteins play crucial roles in biological processes, but are often challenging to study. The NanoDisc platform offers a self-assembled system that solubilizes membrane proteins in water while maintaining their functional activity. NanoDiscs have utility in studying cellular signaling complexes and delivering drugs, showcasing their versatility in biochemistry and pharmacology.
Article
Nanoscience & Nanotechnology
Hyunseok Oh, Younghun Jung, Seokoh Moon, Jaehyeon Hwang, Choongjin Ban, Jinhyo Chung, Woo-Jae Chung, Dae-Hyuk Kweon
Summary: The study developed a method to synthesize dimeric nanodiscs with long-term thermal stability and resistance to aggregation. By controlling oxidation/reduction conditions and lipid-to-protein ratios, the formation of either monomeric or dimeric nanodiscs can be modulated. The dimerization of nanodiscs led to increased antiviral activity, suggesting cooperativity between linked nanodiscs.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Nanoscience & Nanotechnology
Koushambi Mitra, Yamuna Krishnan
Summary: This article presents an elegant method of counting the oligomers in membrane proteins using photobleaching and nanodiscs formed directly from cellular membranes.
NATURE NANOTECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Florian Mahler, Annette Meister, Carolyn Vargas, Gregory Durand, Sandro Keller
Summary: The use of specific amphiphilic molecules can directly assemble lipids and membrane proteins to form native nanodiscs, rather than mixed micelles. Detailed investigation into the lipid bilayer integrity and membrane protein activity in these nanodiscs reveals gentle effects.
Article
Chemistry, Multidisciplinary
David Glueck, Anne Grethen, Manabendra Das, Ogochukwu Patricia Mmeka, Eugenio Perez Patallo, Annette Meister, Ritu Rajender, Stefan Kins, Markus Raeschle, Julian Victor, Ci Chu, Manuel Etzkorn, Zoe Koeck, Frank Bernhard, Jonathan Oyebamiji Babalola, Carolyn Vargas, Sandro Keller
Summary: Membrane proteins can be examined in near-native lipid-bilayer environments with the use of polymer-encapsulated nanodiscs. The creation of electroneutral nanodiscs enables new insights into protein-lipid interactions.
Article
Plant Sciences
Bernd Ackermann, Beatrix Duenschede, Bjoern Pietzenuk, Bo Hojen Justesen, Ute Kraemer, Eckhard Hofmann, Thomas Guenther Pomorski, Danja Schuenemann
Summary: Members of the Oxa1/YidC/Alb3 protein family are involved in the insertion, folding, and assembly of membrane proteins in mitochondria, bacteria, and chloroplasts. The thylakoid membrane protein Alb3 interacts with ribosomes during posttranslational insertion of specific proteins, while Alb4, a homolog located in the same membrane, does not show ribosome binding. Alb3 contacts ribosomes via its C-terminal region and at least one additional binding site within its hydrophobic core.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Erick J. Dufourc
Summary: Membrane nanoobjects such as Bicelles and Nanodiscs are important tools for studying biomembrane properties, providing various membranous platforms for structural biology research. Internal dynamics of these nanoobjects is similar to liposomes, offering potential for studying the 3D structure, topology, and dynamics of membrane proteins.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Chemistry, Medicinal
Lisbeth R. Kjolbye, Leonardo De Maria, Tsjerk A. Wassenaar, Haleh Abdizadeh, Siewert J. Marrink, Jesper Ferkinghoff-Borg, Birgit Schiott
Summary: Nanodisc technology is increasingly used for studying membrane proteins. A new protocol based on geometric equations in Python allows for fast and easy customization of nanodiscs, enabling automation of molecular dynamics simulations. The protocol was validated by simulating seven different nanodiscs, showing good agreement with experimental data and simulation studies.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Irfan Prabudiansyah, Ramon van der Valk, Marie-Eve Aubin-Tam
Summary: FtsH is a membrane-bound protease that plays a crucial role in regulating cellular functions, and can maintain its activity when reconstituted into lipid nanodiscs. Research has shown that the lipid bilayer composition affects the proteolytic activity of FtsH.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Biochemistry & Molecular Biology
Melina Daniilidis, Matthias J. Brandl, Franz Hagn
Summary: Membrane mimetics play a crucial role in studying the structure and function of membrane proteins. In this study, the authors compared the biophysical properties of circularized and linear nanodiscs and found that circularized nanodiscs have improved membrane fluidity and size stability, making them advantageous for high-resolution NMR studies at elevated temperatures.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Laura E. Sperl, Florian Ruehrnoessl, Anita Schiller, Martin Haslbeck, Franz Hagn
Summary: The study used NMR and HDX-MS techniques in lipid nanodiscs to investigate the high-resolution structural changes of Bak in a membrane environment, providing important insights into Bak-mediated membrane permeabilization. Experimental results showed that the alpha-helix 1 element in Bak is a metastable structure contributing to its pro-apoptotic features.
Article
Chemistry, Multidisciplinary
Ralph Maier, Rodrigo Cuevas Arenas, Fajun Zhang, Ana Garcia-Saez, Frank Schreiber
Summary: This study investigates the use of polymer-bounded nanodiscs to study the lipid model system. The size of nanodiscs formed with styrene maleic acid (SMA) is smaller compared to diisobutylene maleic acid (DIBMA). Increasing polymer concentration leads to a decrease in nanodisc size. The stability of nanodiscs formed with SMA is less affected by temperature compared to those formed with DIBMA in phosphate buffer. These findings contribute to the development of protocols for studying membrane proteins in similar membrane mimics.
Article
Chemistry, Multidisciplinary
Bankala Krishnarjuna, Thirupathi Ravula, Ayyalusamy Ramamoorthy
Summary: In this study, the membrane-anchored flavin mononucleotide binding domain (FBD) of CYP450 reductase was extracted in E. coli lipid-nanodiscs using charge-free pentyl-inulin polymer. The FBD in nanodiscs showed conformational homogeneity and enabled high-resolution NMR probing. P-31 NMR revealed that the polymer had no preference for any specific E. coli lipids and identified the lipid types in the nanodiscs.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Lei Sun, Yiyan Yu, Yifei Peng, Dan Wang, Shuyan Wang, Ilkoo Noh, Ronnie H. Fang, Weiwei Gao, Liangfang Zhang
Summary: Platelet membrane-derived nanodiscs (PLT-NDs) have been developed and characterized as platelet decoys for neutralizing biological agents. PLT-NDs effectively neutralize anti-platelet autoantibodies and bacterial virulence factors both in vitro and in vivo, showing significant therapeutic benefits in mouse models. PLT-NDs also demonstrate good biocompatibility and biosafety.
Article
Biochemistry & Molecular Biology
Piotr J. Mak, Ilia G. Denisov
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2018)
Article
Biochemistry & Molecular Biology
Ilia G. Denisov, Yelena Grinkova, Prithviraj Nandigrami, Mrinal Shekhar, Emad Tajkhorshid, Stephen G. Sligar
Correction
Biochemistry & Molecular Biology
Ilia G. Denisov, Yelena V. Grinkova, Prithviraj Nandigrami, Mrinal Shekhar, Emad Tajkhorshid, Stephen G. Sligar
Article
Biochemistry & Molecular Biology
Lada Ivanova, Ilia G. Denisov, Yelena Grinkova, Stephen G. Sligar, Christiane K. Faeste
Article
Biochemical Research Methods
Mark A. McLean, Ilia G. Denisov, Yelena Grinkova, Stephen G. Sligar
ANALYTICAL BIOCHEMISTRY
(2020)
Article
Chemistry, Multidisciplinary
Yilin Liu, Ilia G. Denisov, Yelena V. Grinkova, Stephen G. Sligar, James R. Kincaid
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Review
Biochemistry & Molecular Biology
Stephen G. Sligar, Ilia G. Denisov
Summary: Membrane proteins play crucial roles in biological processes, but are often challenging to study. The NanoDisc platform offers a self-assembled system that solubilizes membrane proteins in water while maintaining their functional activity. NanoDiscs have utility in studying cellular signaling complexes and delivering drugs, showcasing their versatility in biochemistry and pharmacology.
Article
Chemistry, Multidisciplinary
Yilin Liu, Ilia G. Denisov, Stephen G. Sligar, James R. Kincaid
Summary: This study used resonance Raman spectroscopy to compare the effect of Mn-substituted cytochrome b(5) on the oxy complex of CYP17A1, resulting in a specific allosteric interpretation for the more pronounced acceleration seen with the 17OH-PROG substrate. The presence of Mn-b led to a reorientation of a hydrogen bond between the 17OH group of the substrate and the proximal oxygen atom, favoring lyase catalysis, but this effect was not observed for 17OH-pregnenolone.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Ilia G. Denisov, Yelena Grinkova, Tyler Camp, Mark A. McLean, Stephen G. Sligar
Summary: The study demonstrates the impact of midazolam binding at different sites on the metabolism of the drug by human CYP3A4, with implications for drug-drug interactions. The change in the 1OH:4OH metabolism ratio serves as a sensitive probe for drug effects, highlighting the complex interplay between active and allosteric sites in the enzyme.
Article
Biochemistry & Molecular Biology
Yilin Liu, Yelena Grinkova, Michael C. Gregory, Ilia G. Denisov, James R. Kincaid, Stephen G. Sligar
Summary: This study discusses the mechanisms of steroid metabolism in humans, including the role of cytochrome P450, the impact of mutations on metabolism, and the mechanism of bond cleavage reactions. The research reveals that specific mutations can alter enzyme activity, substrate binding modes, and product selectivity.
Article
Spectroscopy
G. S. Denisov, I. G. Denisov
Summary: This study used Birge-Sponer extrapolation to analyze the approximation of the real diatomic molecule potential by the Morse model, estimating the anharmonicity parameter based on transition frequencies. The dependence of the anharmonicity parameter on the vibrational quantum number was calculated for various diatomic molecules, revealing deviations from the Morse model.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2021)
Article
Biochemistry & Molecular Biology
Yilin Liu, Ilia Denisov, Michael Gregory, Stephen G. Sligar, James R. Kincaid
Summary: This study investigates the impact of a CYP17A1 gene mutation on its catalytic activity. The results show that the mutation alters the lyase efficiency by affecting H-bonding interactions and protonation of the reactive ferric peroxo intermediate. The key reaction intermediates are successfully trapped and structurally characterized using cryoradiolysis and resonance Raman techniques.
Article
Biochemistry & Molecular Biology
Ilia G. Denisov, Yelena V. Grinkova, Mark A. McLean, Tyler Camp, Stephen G. Sligar
Summary: Human cytochrome P450 CYP3A4 plays a significant role in the metabolism of more than 35% of pharmaceuticals, leading to drug-drug interactions. This study evaluated the use of midazolam as a probe substrate to detect and predict the involvement of new drug candidates in CYP3A4-mediated drug-drug interactions. The results suggest that the changes in the shape and volume of the substrate-binding pocket explain the occurrence of drug interactions.
Meeting Abstract
Oncology
Zhijun Guo, Jianxun Lei, Kwon Ho Hong, Beverly Norris, Craig M. Flory, Swaathi Jayaraman, Connor McDermott, Elizabeth Ambrose, Irina Sevrioukova, Tom Poulos, Ilia Denisov, Stephen Sliga, Robert J. Schumacher, Gunda I. Georg, John R. Hawse, Matthew P. Goetz, David A. Potter
Article
Biochemistry & Molecular Biology
Ilia G. Denisov, Javier L. Baylon, Yelena V. Grinkova, Emad Tajkhorshid, Stephen G. Sligar