Review
Chemistry, Multidisciplinary
Sem Tamara, Maurits A. den Boer, Albert J. R. Heck
Summary: Native mass spectrometry is a method for analyzing and characterizing macromolecules while preserving their native structural features. It has experienced significant growth in the past decade, especially in enhancing sensitivity and resolving power, and has a wide range of applications.
Review
Chemistry, Multidisciplinary
Emilia Christofi, Perdita Barran
Summary: The investigation of macromolecular biomolecules with ion mobility mass spectrometry (IM-MS) techniques has provided substantial insights into the field of structural biology. An IM-MS workflow can provide mass, charge, and conformation information of a given target analyte, which is crucial for studying protein structures. This review focuses on the analysis of proteins and their complexes using IM-MS, discussing the typical features of an IM-MS experiment and how the data can be interpreted and compared with computational tools. The review also highlights the benefits of coupling mobility analysis to activation methods and its application to the study of conformationally dynamic and intrinsically disordered proteins.
Review
Chemistry, Multidisciplinary
Dalton T. Snyder, Sophie R. Harvey, Vicki H. Wysocki
Summary: Native mass spectrometry (nMS) is an important tool in structural biology, with great potential due to a range of ionization techniques and new hybrid ion mobility and mass spectrometry systems. This review focuses on the key features and advantages of surface collisions (surface-induced dissociation, SID) for probing connectivity in protein and nucleoprotein complexes, demonstrating the importance of SID and nMS in future structural elucidation of biological assemblies.
Article
Chemistry, Multidisciplinary
Luis A. Macias, Xun Wang, Bryan W. Davies, Jennifer S. Brodbelt
Summary: This study applied UVPD to probe the paratopes of nanobodies and successfully located the antigen binding sites and intermolecular salt-bridges. This expands the capabilities of UVPD as a new strategy for characterization of nanobodies.
Article
Chemistry, Analytical
Elnaz Aliyari, Lars Konermann
Summary: Native electrospray ionization (ESI)-mass spectrometry (MS) is commonly used for detecting and characterizing multi-protein complexes, however, nonspecific protein clustering in the ESI plume can distort results. This study combines experiments and molecular dynamics simulations to reveal insights into ESI clustering of proteins, demonstrating the formation of nonspecific protein clusters via solvent evaporation. Through MD simulations, the study confirms the viability of charged residue model (CRM) and ion evaporation model (IEM) pathways for protein clustering.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Analytical
Anthony M. Pitts-McCoy, Abdirahman M. Abdillahi, Kenneth W. Lee, Scott A. McLuckey
Summary: Native mass spectrometry (MS) using negative-ion polarity facilitates charge state determination in heterogeneous mixtures by attaching multiply charged ions. This approach provides broad mass-to-charge ratio information and overcomes challenges associated with narrow charge state distributions. The utility of multiply charged cation attachment is demonstrated in the analysis of complex ions and mixtures, enabling precise charge state assignments and revealing missing components.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Wenjin Cao, Qinqin Yuan, Hanhui Zhang, Xiaoguo Zhou, Steven R. Kass, Xue-Bin Wang
Summary: We conducted a study on glycine-chloride/bromide complexes (Gly center dot X-, X = Cl/Br) using negative ion photoelectron spectroscopy and quantum chemical computations, comparing them with the previously studied Gly center dot I- cluster ion. Through experimental and theoretical analysis, we found that different Gly center dot X- complexes adopt the same types of low-lying isomers with varying relative energies. Despite the congested spectral profiles, spectral assignments for Gly center dot Cl- and Gly center dot Br- were accomplished with the guidance from Gly center dot I-, which has well-resolved spectral peaks. This study investigates the binding patterns of glycine complexes with different halides, demonstrating that iodide-tagging is an effective spectroscopic method for unraveling diverse ion-molecule binding motifs in cluster anions with congested spectral bands.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Biochemical Research Methods
Alexander I. M. Sever, Victor Yin, Lars Konermann
Summary: Various activation methods are available for the fragmentation of gaseous protein complexes produced by electrospray ionization. Collision-induced dissociation (CID) is the most widely used fragmentation technique, but it often results in the ejection of highly charged monomers without providing structural insights. Experimental data on hemoglobin complexes show that structurally informative subcomplexes can be generated by CID under certain conditions, depending on the fate of protein-protein interfaces after transfer into the gas phase.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Article
Chemistry, Analytical
Justin T. Seffernick, S. M. Bargeen Ala m Turzo, Sophie R. . Harvey, Yongseok Kim, Arpad Somogyi, Shir Marciano, Vicki H. Wysocki, Steffen Lindert
Summary: Understanding the relationship between protein structure and experimental data is crucial. In this study, a method was developed to predict the full energy-resolved mass spectrometry (ERMS) plot from the structure. The results showed that the accuracy of predictions depended on the quality of the native crystal structures.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Niklas Geue, Tom S. Bennett, Alexandra-Ana-Maria Arama, Lennart A. I. Ramakers, George F. S. Whitehead, Grigore A. Timco, P. B. Armentrout, Eric J. L. McInnes, Neil A. Burton, Richard E. P. Winpenny, Perdita E. Barran
Summary: This study investigates the disassembly mechanisms and energetics of a series of heterometallic rings and ro-taxanes using ion mobility mass spectrometry and density functional theory. It shows that the stability of these complexes can be tuned by altering the metal composition and end groups.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Analytical
Moujun Luan, Zhuanghao Hou, Buchun Zhang, Likun Ma, Siming Yuan, Yangzhong Liu, Guangming Huang
Summary: In this study, the dumbbell-shaped calmodulin was chosen as a multi-domain protein model to investigate the structural evolution during electrospray ionization (ESI) process. The results showed that the protein followed the classical charge residue model and the apo-calmodulin underwent unfolding during the early evaporation stage. This study proposed a novel ESI mechanism called the domain repulsion model, which provides new mechanistic insights for the exploration of proteins with more domains.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Kimberly C. Fabijanczuk, Weam A. O. Altalhi, Asma M. O. Aldajani, Allan J. Canty, Scott A. McLuckey, Richard A. J. O'Hair
Summary: In this study, gas-phase reactions between tris-1,10-phenantholine metal dications and tetraphenylborate anions were investigated. The formation of ion-pairs and subsequent organometallic complex formation were observed. DFT calculations confirmed the energy barriers and hydrolysis reactions in accordance with experimental results.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Multidisciplinary
Duong T. Bui, Zhixiong Li, Pavel I. Kitov, Ling Han, Elena N. Kitova, Marlene Fortier, Camille Fuselier, Philippine Granger Joly de Boissel, David Chatenet, Nicolas Doucet, Stephen M. Tompkins, Yves St-Pierre, Lara K. Mahal, John S. Klassen
Summary: Electrospray ionization mass spectrometry (ESI-MS) is a powerful label-free assay for detecting noncovalent biomolecular complexes and quantifying binding thermochemistry. However, the assumption that the ion signals of free and bound species in ESI-MS measurements can quantitatively reflect their relative concentrations is only valid when their response factors are similar.
ACS CENTRAL SCIENCE
(2022)
Article
Chemistry, Physical
Steven Daly, Sebastian Weske, Antonija Mravak, Marjan Krstic, Alexander Kulesza, Rodolphe Antoine, Vlasta Bonacic-Koutecky, Philippe Dugourd, Konrad Koszinowski, Richard A. J. O'Hair
Summary: Electrospray ionization of phenyl argentates formed by transmetalation reactions between phenyl lithium and silver cyanide enables access to argentate aggregates, [AgnPhn+1](-), which exhibit a strong bathochromic shift in optical spectra with increasing size. Theoretical calculations aid in assigning the experimental UVPD spectra to specific isomers and provide insights into the transition from 2D to 3D structure of the metallic component as the complex size increases. These aggregates do not possess pronounced metallic cluster properties or ligated metallic cluster features, representing novel organometallic characteristics built from Ag2Ph subunits.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Review
Chemistry, Multidisciplinary
Amber D. Rolland, James S. Prell
Summary: Native mass spectrometry is a method to preserve and determine the native structure, composition, and stoichiometry of biomolecules and their complexes after they are transferred into the gas phase. Recent advancements in instrumentation and experimental methods have allowed for the analysis of more complex and heterogeneous samples, providing insights into the structure and function of these biomolecules. However, the heterogeneity of the samples poses challenges in assigning ion mass, charge, composition, and structure, which can be addressed using deconvolution algorithms and tools.
Article
Chemistry, Analytical
Sophie R. Harvey, Carla O'Neale, Kevin L. Schey, Vicki H. Wysocki
Summary: Aquaporin-0 (AQP0) is the most abundant membrane protein in the eye lens, and its post-translational modifications can accumulate with age. Native mass spectrometry and surface-induced dissociation can be used to study these modifications.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sheng Zhang, Stan Yoo, Dalton T. Snyder, Benjamin B. Katz, Amy Henrickson, Borries Demeler, Vicki H. Wysocki, Adam G. Kreutzer, James S. Nowick
Summary: A beta dimers are neurotoxic and pathologically relevant species in Alzheimer's disease. This paper introduces a stable A beta(C18C33) dimer model that forms pure dimers in lipid environments without aggregation into fibrils. This model is important for amyloid and Alzheimer's disease research.
Review
Chemistry, Multidisciplinary
Dalton T. Snyder, Sophie R. Harvey, Vicki H. Wysocki
Summary: Native mass spectrometry (nMS) is an important tool in structural biology, with great potential due to a range of ionization techniques and new hybrid ion mobility and mass spectrometry systems. This review focuses on the key features and advantages of surface collisions (surface-induced dissociation, SID) for probing connectivity in protein and nucleoprotein complexes, demonstrating the importance of SID and nMS in future structural elucidation of biological assemblies.
Article
Biochemistry & Molecular Biology
Kye Stachowski, Andrew S. Norris, Devante Potter, Vicki H. Wysocki, Mark P. Foster
Summary: In this study, the mechanism of Cre recombinase assembly was revealed, which allows for DNA recognition and specific cleavage through a series of intermediates. The results show the importance of protein and DNA flexibility in site selection and recombination efficiency mediated by Cre.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Analytical
Henriette Krenkel, Jeffery Brown, Keith Richardson, Emmy Hoyes, Michael Morris, Rainer Cramer
Summary: Mass spectrometry enables automated analysis of complex samples without labeling. Liquid atmospheric pressure matrix-assisted laser desorption/ionization (LAP-MALDI) allows for rapid sample preparation and high-speed mass spectrometry analysis. This technology achieves a significant increase in analysis speed, has high ion signal stability, and can analyze multiply charged peptide ions at extreme speeds.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Justin T. Seffernick, S. M. Bargeen Ala m Turzo, Sophie R. . Harvey, Yongseok Kim, Arpad Somogyi, Shir Marciano, Vicki H. Wysocki, Steffen Lindert
Summary: Understanding the relationship between protein structure and experimental data is crucial. In this study, a method was developed to predict the full energy-resolved mass spectrometry (ERMS) plot from the structure. The results showed that the accuracy of predictions depended on the quality of the native crystal structures.
ANALYTICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
S. M. Bargeen Alam Turzo, Justin T. Seffernick, Amber D. Rolland, Micah T. Donor, Sten Heinze, James S. Prell, Vicki H. Wysocki, Steffen Lindert
Summary: This study develops an algorithm to predict protein collision cross sections (CCS) and integrates experimental ion mobility data into Rosetta-based molecular modeling to predict protein structures from sequence.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Biochemical Research Methods
Vicki Wysocki
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Biochemistry & Molecular Biology
Weicheng Li, Andrew S. Norris, Katie Lichtenthal, Skyler Kelly, Elihu C. Ihms, Paul Gollnick, Vicki H. Wysocki, Mark P. Foster
Summary: Homo-oligomeric ligand-activated proteins are widely present in biology and their functions are regulated by allosteric coupling between ligand-binding sites. By combining statistical thermodynamic modeling with native mass spectrometry, the effects of ligand-dependent population shifts and coupling free energy terms can be quantified, providing necessary insights into regulation and enabling a better understanding of cooperativity.
Editorial Material
Biochemical Research Methods
Vicki H. Wysocki
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Biochemistry & Molecular Biology
Sravya Kovvali, Yuan Gao, Austin Cool, Steffen Lindert, Vicki H. Wysocki, Charles E. Bell, Venkat Gopalan
Summary: Amadori rearrangement products are stable sugar-amino acid conjugates that are formed nonenzymatically during food processing. Understanding bacterial utilization of these fructosamines is crucial due to their impact on the animal gut microbiome. In this study, the catalytic mechanism of the deglycase enzyme FrlB was elucidated through crystallography, computational docking, biochemical assays, and native mass spectrometry. The findings provide insights into the structure-function relationship and mechanisms of enzymes.
Article
Chemistry, Multidisciplinary
Thomas Walker, He Mirabel Sun, Tiffany Gunnels, Vicki Wysocki, Arthur Laganowsky, Hays Rye, David Russell
Summary: Variable-temperature electrospray ionization (vT-ESI) native mass spectrometry (nMS) is used to investigate the thermodynamics of ATP binding to the GroEL tetradecamer chaperonin complex. The study reveals strong enthalpy-entropy compensation (EEC) and variations in stepwise free energy changes, which are consistent with the established nested cooperativity model of GroEL-ATP interactions. The entropy-driven ATP binding is attributed to ligand-induced conformational changes and reorganization of water molecules within the GroEL complex.
ACS CENTRAL SCIENCE
(2023)
Article
Biochemical Research Methods
Mengxuan Jia, Yang Song, Chen Du, Vicki H. Wysocki
Summary: The charge partitioning during the dissociation of protein complexes in the gas phase is influenced by various factors, including interfacial interactions, protein flexibility, protein conformation, and dissociation methods. This study used two cysteine-containing homodimer proteins to investigate the charge partitioning behaviors of collision-induced dissociation (CID) and surface-induced dissociation (SID) processes. Results showed that restructuring dominates with CID, while dissociation with symmetric charge partitioning dominates with SID, regardless of the oxidation state of the intramolecular disulfide bonds. Gas collisions reveal the charge-dependent restructuring/unfolding properties of the protein precursor, while surface collisions predominantly lead to more charge-symmetric monomer separation.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Editorial Material
Biochemical Research Methods
Jenny Brodbelt, Vicki Wysocki
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Editorial Material
Biochemical Research Methods
John C. C. Tran, Iain D. G. Campuzano, Erin S. S. Baker, Vicki H. H. Wysocki
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)