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
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
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
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
Amanda Pritzlaff, Guillaume Ferre, Emma Mulry, Ling Lin, Niloofar Gopal Pour, Daniel A. Savin, Michael E. Harris, Matthew T. Eddy
Summary: PEGylation is a promising method to improve protein stability, but the underlying mechanism is not well understood. This study used a structural and biophysical approach to investigate the effects of PEGylation on the carbohydrate recognition domain of human galectin-3. The results revealed the potential role of charged residues in PEG localization and provided insights for the rational design of conjugates.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
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
Giovanna Viola, Carlo Giorgio Barracchia, Roberto Tira, Francesca Parolini, Giulia Leo, Massimo Bellanda, Francesca Munari, Stefano Capaldi, Mariapina D'Onofrio, Michael Assfalg
Summary: Understanding the interactions between nanoparticles and proteins is crucial for their successful application in biology. This study reveals a new type of nano-bio interaction, where ultrasmall gold nanoparticles form stable multimolecular assemblies with intrinsically disordered proteins. This finding has important implications for the targeting of aberrant protein aggregation in cells.
Article
Biochemistry & Molecular Biology
Alan J. Situ, Tobias S. Ulmer
Summary: Membrane proteins are commonly studied in artificial membrane systems that do not accurately represent the native cell membranes. In this study, the thermodynamic stability of a specific transmembrane complex was compared between large unilamellar vesicles (LUVs) and bicelles. It was found that LUVs provide modestly superior stabilization for the transmembrane complex, but bicelles still perform well. Additionally, the introduction of a specific mutation alleviated the destabilization caused by another mutation, indicating the involvement of weak hydrogen bonding.
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.
Review
Biochemistry & Molecular Biology
Matthew J. Laurence, Timothy S. Carpenter, Ted A. Laurence, Matthew A. Coleman, Megan Shelby, Chao Liu
Summary: Proteins embedded in biological membranes play important roles in organisms and are targets for many drugs. However, purifying these insoluble proteins has been challenging, making their detailed characterization difficult. The development of nanodisc techniques and fluorescence correlation spectroscopy (FCS) has provided new methods for studying membrane proteins. This review summarizes the current nanodisc techniques and FCS fundamentals, and discusses studies that have used FCS and nanodisc technology to investigate various membrane proteins.
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
Multidisciplinary Sciences
Gerard Duart, Assaf Elazar, Jonathan Y. Weinstein, Laura Gadea-Salom, Juan Ortiz-Mateu, Sarel J. Fleishman, Ismael Mingarro, Luis Martinez-Gil
Summary: Several methods have been developed to explore protein-protein interactions, but there is a need for more research on targeting transmembrane domains (TMDs). This study developed a computational approach to design sequences that can modulate protein-protein interactions in the membrane, and successfully applied it to BclxL. The findings enhance our understanding of protein-protein interactions in membranes and may lead to the development of inhibitors targeting TMD interactions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
Chemistry, Analytical
Deseree J. Reid, Tapasyatanu Dash, Zhihan Wang, Craig A. Aspinwall, Michael T. Marty
Summary: In this study, native mass spectrometry (MS) and fast photochemical oxidation of peptides (FPOP) were used to investigate the interactions between the antibiotic daptomycin and different lipid bilayer nanodiscs. The results showed that daptomycin incorporates randomly into bilayers and has stronger interactions with rigid membranes. Pore formation may occur in fluid membranes, exposing daptomycin to oxidation. These findings demonstrate the complementarity of native MS, FPOP, and membrane conductance experiments in understanding antibiotic peptide-membrane interactions.
ANALYTICAL CHEMISTRY
(2023)
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
Biochemistry & Molecular Biology
Meng Zhang, Miao Gui, Zi-Fu Wang, Christoph Gorgulla, James J. Yu, Hao Wu, Zhen-yu J. Sun, Christoph Klenk, Lisa Merklinger, Lena Morstein, Franz Hagn, Andreas Pluckthun, Alan Brown, Mahmoud L. Nasr, Gerhard Wagner
Summary: Recent studies have uncovered the complex interactions between neurotensin receptor 1, neurotensin, and G proteins in a lipid bilayer environment, revealing a more intricate network of protein-protein interactions compared to structures obtained in detergent micelles. These findings provide new insights into the modulation of complex formation by lipid membranes and propose an allosteric mechanism for GDP release in G protein activation.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Srikar Munukutla, Alec Bertoy, Stephen Rush, Ayyalusamy Ramamoorthy
Summary: This study presents a method to convert NMR spectra into piano notes and create a library of molecule-inspired tunes. This supplementary approach can contribute to a more inclusive learning atmosphere for all students in the classroom.
JOURNAL OF CHEMICAL EDUCATION
(2022)
Article
Chemistry, Physical
Bankala Krishnarjuna, Magdalena I. Ivanova, Ayyalusamy Ramamoorthy
Summary: DPRs play crucial roles in ALS and FTD, with (GA)6 and (GR)6 forming neurotoxic aggregates while (GP)6 does not aggregate. Feasibility of high-resolution monitoring of peptide aggregation was explored using NMR experiments, demonstrating the ability to detect minor conformational changes and aggregation kinetics.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Chemistry, Physical
Samuel D. McCalpin, Thirupathi Ravula, Ayyalusamy Ramamoorthy
Summary: This study demonstrates the formation of lipid nanodiscs using nonionic glycoside natural products called saponins and phospholipid DMPC. The effect of different saponin/lipid ratios on the properties of nanodiscs was investigated. The results show that a high saponin/lipid ratio reduces the size of nanodiscs and decreases their ability to align in a magnetic field.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Thirupathi Ravula, Ayyalusamy Ramamoorthy
Summary: Recent advances in lipid nanodisc technology have addressed challenges in studying membrane proteins and drug delivery. Using synthetic amphiphilic polymers, researchers successfully aligned large-size polymer nanodiscs for high-resolution solid-state NMR studies. The use of polymer-based macro-nanodiscs as alignment media has further enabled structural studies on proteins by solution NMR spectroscopy.
Review
Biochemistry & Molecular Biology
Bankala Krishnarjuna, Ayyalusamy Ramamoorthy
Summary: Atomic-resolution structural studies of membrane-associated proteins and peptides in a membrane environment are important for understanding their biological function and disease pathology. Recent advancements in NMR spectroscopy, cryoEM approaches, and the development of novel membrane mimetics have overcome the complexity of the cell membrane and enabled reconstitution and investigation of membrane proteins.
Article
Chemistry, Analytical
Bankala Krishnarjuna, Sang -Ghoul Im, Thirupathi Ravula, Joseph Marte, Richard J. Auchus, Ayyalusamy Ramamoorthy
Summary: This study reports the successful functional reconstitution of a membrane-bound redox complex in non-ionic inulin-based polymer nanodiscs. The nanodiscs have a higher phase-transition temperature and can align in an externally applied magnetic field. These findings suggest that non-ionic polymer nanodiscs can be used for studying the function and structures of various membrane proteins/complexes.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yoel A. Klug, Roland Schwarzer, Thirupathi Ravula, Etai Rotem, Ayyalusamy Ramamoorthy, Yechiel Shai
Summary: In this study, calcium interaction motifs (CIMs) in the gp41 CHR and NHR regions were discovered via NMR spectroscopy. The assembly of CHR-NHR SHB was found to be facilitated in Ca2+-containing media and impaired in CIM mutants. The clinically approved fusion inhibitor T20 exhibited reduced inhibitory efficiency when challenged with calcium, which could have implications for the development of better fusion inhibitors for HIV.
Review
Chemistry, Multidisciplinary
Yusuke Nishiyama, Guangjin Hou, Vipin Agarwal, Yongchao Su, Ayyalusamy Ramamoorthy
Summary: Solid-state NMR spectroscopy is a commonly used technique for studying the atomic-resolution structure and dynamics of various systems. However, its spectral resolution and sensitivity have been limited. The development of ultrafast-MAS technology has provided opportunities to improve the resolution and sensitivity of solid samples. Despite the limitations and challenges, ultrafast-MAS NMR techniques have achieved remarkable results in various fields.
Article
Biochemistry & Molecular Biology
Bankala Krishnarjuna, Thirupathi Ravula, Edgar M. Faison, Marco Tonelli, Qi Zhang, Ayyalusamy Ramamoorthy
Summary: In this study, polymer-based nanodiscs were used to measure RDCs from nucleic acids. The nanodiscs were characterized and their alignment stability was confirmed. RDCs from a labeled nucleic acid molecule were successfully measured using the aligned nanodiscs. This demonstrates the potential of SMA-EA-based lipid-nanodiscs for structural and dynamical studies of nucleic acids.
Article
Chemistry, Multidisciplinary
Pei Yang, Wen Guo, Ayyalusamy Ramamoorthy, Zhan Chen
Summary: There is significant interest in developing antimicrobial compounds to overcome bacterial resistance to conventional antibiotics. MSI-594 is a synthetic peptide with broad spectrum antimicrobial activity. Investigating how MSI-594 disrupts the cell membrane is important for understanding its mechanism of action.
Article
Chemistry, Physical
Samuel D. McCalpin, Malitha C. Dickwella Widanage, Riqiang Fu, Ayyalusamy Ramamoorthy
Summary: We developed a new method using magic angle spinning (MAS) to produce stable intermediates of the islet amyloid polypeptide associated with type-2 diabetes. These intermediates were a heterogeneous mixture of globular and rod-like species with beta-sheet structure and the ability to seed fibrillation. Our findings suggest that this methodology can be applied to studying other aggregating systems.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Materials Science, Multidisciplinary
Jiwon Lim, Shuo Zhang, Luyang Wang, Deokwon Seo, Malitha C. Dickwella Widanage, Kevin P. Pipe, Ayyalusamy Ramamoorthy, Jinsang Kim
Summary: DHI-free PCA coating using 3,4-dihydroxybenzylamine hydrobromide provides a smooth and uniform surface with preserved primary amine groups, offering an alternative strategy for surface amine functionalization. Additionally, DHI-free PCA improves the thermal conductivity of graphene-polymer composites.
ACS APPLIED POLYMER MATERIALS
(2023)
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
Thirupathi Ravula, Ayyalusamy Ramamoorthy
Summary: A family of non-ionic amphiphilic polymers synthesized by hydrophobic functionalization of fructo-oligosaccharides/inulin is reported, which enhances the interaction efficiency between lipid nanodiscs and proteins, and exhibits stability, alignment properties, and unprecedented efficiency in extracting membrane proteins.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
