Structural characterisation of medically relevant protein assemblies by integrating mass spectrometry with computational modelling.

Structural mass spectrometry with its various techniques is a powerful tool for the structural elucidation of medically relevant protein assemblies. It delivers information on the composition, stoichiometries, interactions and topologies of these assemblies. Most importantly it can deal with heterogeneous mixtures and assemblies which makes it universal among the conventional structural techniques. In this review we summarise recent advances and challenges in structural mass spectrometric techniques. We describe how the combination of the different mass spectrometry-based methods with computational strategies enable structural models at molecular levels of resolution. These models hold significant potential for helping us in characterizing the function of protein assemblies related to human health and disease. SIGNIFICANCE In this review we summarise the techniques of structural mass spectrometry often applied when studying protein-ligand complexes. We exemplify these techniques through recent examples from literature that helped in the understanding of medically relevant protein assemblies. We further provide a detailed introduction into various computational approaches that can be integrated with these mass spectrometric techniques. Last but not least we discuss case studies that integrated mass spectrometry and computational modelling approaches and yielded models of medically important protein assembly states such as fibrils and amyloids.

• Publication year

  2017

• Venue

  Journal of Proteomics

• Publication date

  2017-04-28

• Fields of study

  Biology, Medicine, Chemistry, Computer Science

• Identifiers
  DOI 10.1016/j.jprot.2017.04.019PMID 28461040
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• A mass spectrometry– based hybrid method for structural modeling of protein complexes

  2018cited by this paper
• “Zooming With”

  2018cited by this paper
• Protein-protein interactions: scoring schemes and binding affinity.

  2017cited by this paper
• A Residue-Resolved Bayesian Approach to Quantitative Interpretation of Hydrogen-Deuterium Exchange from Mass Spectrometry: Application to Characterizing Protein-Ligand Interactions.

  2017cited by this paper
• The role of interfacial lipids in stabilizing membrane protein oligomers

  2017cited by this paper
• Surface Accessibility and Dynamics of Macromolecular Assemblies Probed by Covalent Labeling Mass Spectrometry and Integrative Modeling

  2017cited by this paper
• An infrared spectroscopy approach to follow β-sheet formation in peptide amyloid assemblies.

  2017cited by this paper
• Mass spectrometry captures off-target drug binding and provides mechanistic insights into the human metalloprotease ZMPSTE24

  2016cited by this paper
• Monitoring Solution Structures of Peroxisome Proliferator-Activated Receptor β/δ upon Ligand Binding

  2016cited by this paper
• Blind testing of cross‐linking/mass spectrometry hybrid methods in CASP11

  2016cited by this paper
• Ultraviolet Photodissociation of Native Proteins Following Proton Transfer Reactions in the Gas Phase.

  2016cited by this paper
• Infrared Laser Activation of Soluble and Membrane Protein Assemblies in the Gas Phase.

  2016cited by this paper
• Elucidation of tonic and activated B-cell receptor signaling in Burkitt’s lymphoma provides insights into regulation of cell survival

  2016cited by this paper
• A sliding selectivity scale for lipid binding to membrane proteins.

  2016cited by this paper
• Mass spectrometry guided structural biology.

  2016cited by this paper
• Hybrid Mass Spectrometry: Towards Characterization of Protein Conformational States.

  2016cited by this paper
• Crosslinking and Mass Spectrometry: An Integrated Technology to Understand the Structure and Function of Molecular Machines.

  2016cited by this paper
• Automated structure modeling of large protein assemblies using crosslinks as distance restraints

  2016cited by this paper
• Mass-spectrometric exploration of proteome structure and function

  2016cited by this paper
• Molecular architecture of the human U4/U6.U5 tri-snRNP

  2016cited by this paper
• Symmetry of Charge Partitioning in Collisional and UV Photon-Induced Dissociation of Protein Assemblies

  2016cited by this paper
• Molecular architecture of the Saccharomyces cerevisiae activated spliceosome

  2016cited by this paper
• Quantitative cross-linking/mass spectrometry reveals subtle protein conformational changes

  2016cited by this paper
• Allosteric Inhibition of Anti-Apoptotic MCL-1

  2016cited by this paper
• EM∩IM: software for relating ion mobility mass spectrometry and electron microscopy data.

  2016cited by this paper
• The role of protein and peptide separation before mass spectrometry analysis in clinical proteomics.

  2015cited by this paper
• The complete structure of the 55S mammalian mitochondrial ribosome

  2015cited by this paper
• Early stages of insulin fibrillogenesis examined with ion mobility mass spectrometry and molecular modelling

  2015cited by this paper
• A strategy for dissecting the architectures of native macromolecular assemblies

  2015cited by this paper
• Peroxisome proliferator-activated receptors as targets to treat non-alcoholic fatty liver disease.

  2015cited by this paper
• Chemical cross‐linking and native mass spectrometry: A fruitful combination for structural biology

  2015cited by this paper
• Mass spectrometry of protein complexes: from origins to applications.

  2015cited by this paper
• A subset of annular lipids is linked to the flippase activity of an ABC transporter.

  2015cited by this paper
• The Impact II, a Very High-Resolution Quadrupole Time-of-Flight Instrument (QTOF) for Deep Shotgun Proteomics*

  2015cited by this paper
• Topological Models of Heteromeric Protein Assemblies from Mass Spectrometry: Application to the Yeast eIF3:eIF5 Complex

  2015cited by this paper
• Bayesian deconvolution of mass and ion mobility spectra: from binary interactions to polydisperse ensembles.

  2015cited by this paper
• Getting to the core of protein pharmaceuticals--Comprehensive structure analysis by mass spectrometry.

  2015cited by this paper
• Quantifying the stabilizing effects of protein–ligand interactions in the gas phase

  2015cited by this paper
• Uncovering the Early Assembly Mechanism for Amyloidogenic β2-Microglobulin Using Cross-linking and Native Mass Spectrometry*

  2015cited by this paper
• Electron transfer dissociation provides higher‐order structural information of native and partially unfolded protein complexes

  2015cited by this paper
• Dynamic protein ligand interactions – insights from MS

  2014cited by this paper
• Architecture and conformational switch mechanism of the ryanodine receptor

  2014cited by this paper
• A draft map of the human proteome

  2014cited by this paper
• Membrane proteins bind lipids selectively to modulate their structure and function

  2014cited by this paper
• Mass-spectrometry-based draft of the human proteome

  2014cited by this paper
• Defining the Stoichiometry and Cargo Load of Viral and Bacterial Nanoparticles by Orbitrap Mass Spectrometry

  2014cited by this paper
• A mass spectrometry-based hybrid method for structural modelling of protein complexes

  2014cited by this paper
• Molecular Architecture of the 40S⋅eIF1⋅eIF3 Translation Initiation Complex

  2014cited by this paper
• Top Down proteomics: facts and perspectives.

  2014cited by this paper
• Amphitrite: A program for processing travelling wave ion mobility mass spectrometry data

  2013cited by this paper
• Impact of charge state on gas-phase behaviors of noncovalent protein complexes in collision induced dissociation and surface induced dissociation.

  2013cited by this paper
• The coming age of complete, accurate, and ubiquitous proteomes.

  2013cited by this paper
• Status of Large-scale Analysis of Post-translational Modifications by Mass Spectrometry*

  2013cited by this paper
• Mass spectrometric protein maps for biomarker discovery and clinical research

  2013cited by this paper
• Comparative cross-linking and mass spectrometry of an intact F-type ATPase suggest a role for phosphorylation

  2013cited by this paper
• Quantitative mass spectrometry in proteomics: critical review update from 2007 to the present

  2012cited by this paper
• Investigation of protein-RNA interactions by mass spectrometry--Techniques and applications.

  2012cited by this paper
• Massign: an assignment strategy for maximizing information from the mass spectra of heterogeneous protein assemblies.

  2012cited by this paper
• INAUGURAL ARTICLE by a Recently Elected Academy Member:Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach

  2012cited by this paper
• Identification of cross-linked peptides from complex samples

  2012cited by this paper
• Putting the Pieces Together: Integrative Modeling Platform Software for Structure Determination of Macromolecular Assemblies

  2012cited by this paper
• Structural modeling of heteromeric protein complexes from disassembly pathways and ion mobility-mass spectrometry.

  2012cited by this paper
• StavroX—A Software for Analyzing Crosslinked Products in Protein Interaction Studies

  2011cited by this paper
• A protein complex network of Drosophila melanogaster.

  2011cited by this paper
• Mass Spectrometry of Intact V-Type ATPases Reveals Bound Lipids and the Effects of Nucleotide Binding

  2011cited by this paper
• Structure-based discovery of prescription drugs that interact with the norepinephrine transporter, NET

  2011cited by this paper
• Regulation of BCR signaling.

  2011cited by this paper
• The polydispersity of αB-crystallin is rationalized by an interconverting polyhedral architecture.

  2011cited by this paper
• The beginning of a beautiful friendship: Cross-linking/mass spectrometry and modelling of proteins and multi-protein complexes

  2011cited by this paper
• Integrative Structure Modeling of Macromolecular Assemblies from Proteomics Data*

  2010cited by this paper
• Integrating Ion Mobility Mass Spectrometry with Molecular Modelling to Determine the Architecture of Multiprotein Complexes

  2010cited by this paper
• Decoding signalling networks by mass spectrometry-based proteomics

  2010cited by this paper
• Generating and navigating proteome maps using mass spectrometry

  2010cited by this paper
• Database search algorithm for identification of intact cross-links in proteins and peptides using tandem mass spectrometry.

  2010cited by this paper
• Elongated oligomers in β2-microglobulin amyloid assembly revealed by ion mobility spectrometry-mass spectrometry

  2010cited by this paper
• Mass-spectrometry-based clinical proteomics--a review and prospective.

  2010cited by this paper
• Hydrogen exchange mass spectrometry: what is it and what can it tell us?

  2010cited by this paper
• The landscape of somatic copy-number alteration across human cancers

  2010cited by this paper
• Mass spectrometry–based proteomics in cell biology

  2010cited by this paper
• Modification‐specific proteomics: Strategies for characterization of post‐translational modifications using enrichment techniques

  2009cited by this paper
• Mass spectrometry in clinical proteomics – from the present to the future

  2008cited by this paper
• Mass spectrometry for proteomics.

  2008cited by this paper
• Native mass spectrometry: a bridge between interactomics and structural biology

  2008cited by this paper
• Integrating diverse data for structure determination of macromolecular assemblies.

  2008cited by this paper
• Multidimensional LC separations in shotgun proteomics.

  2008cited by this paper
• Identification of cross-linked peptides from large sequence databases

  2008cited by this paper
• Stability and shape of hepatitis B virus capsids in vacuo.

  2008cited by this paper
• Large-scale mapping of human protein–protein interactions by mass spectrometry

  2007cited by this paper
• Quantitative mass spectrometry in proteomics: a critical review

  2007cited by this paper
• The role of mass spectrometry in structure elucidation of dynamic protein complexes.

  2007cited by this paper
• A high-quality catalog of the Drosophila melanogaster proteome

  2007cited by this paper
• FireDock: Fast interaction refinement in molecular docking

  2007cited by this paper
• Global landscape of protein complexes in the yeast Saccharomyces cerevisiae

  2006cited by this paper
• Hydrogen exchange mass spectrometry for the analysis of protein dynamics.

  2006cited by this paper
• Proteome survey reveals modularity of the yeast cell machinery

  2006cited by this paper
• Chemical cross-linking and mass spectrometry to map three-dimensional protein structures and protein-protein interactions.

  2006cited by this paper
• Status of complete proteome analysis by mass spectrometry: SILAC labeled yeast as a model system

  2006cited by this paper
• Therapeutic roles of peroxisome proliferator-activated receptor agonists.

  2005cited by this paper
• PatchDock and SymmDock: servers for rigid and symmetric docking

  2005cited by this paper
• The abc's (and xyz's) of peptide sequencing

  2004cited by this paper

• Computational methods for advanced mass spectrometry – a review

  2025cites this paper
• A Tutorial Review of Labeling Methods in Mass Spectrometry-Based Quantitative Proteomics

  2024cites this paper
• The Cdc48 N-terminal domain has a molecular switch that mediates the Npl4-Ufd1-Cdc48 complex formation.

  2023cites this paper
• Current proteomics methods applicable to dissecting the DNA damage response

  2023cites this paper
• A special issue of Essays in Biochemistry on structural mass spectrometry

  2023cites this paper
• Using mass spectrometry-based methods to understand amyloid formation and inhibition of alpha-synuclein and amyloid beta.

  2022cites this paper
• Integrative Mass Spectrometry-Based Approaches for Modeling Macromolecular Assemblies.

  2021cites this paper
• Structural Proteomics Methods to Interrogate the Conformations and Dynamics of Intrinsically Disordered Proteins

  2021cites this paper
• Multiprotein Complexes: Methods and Protocols

  2021cites this paper
• Exploring the structure and dynamics of macromolecular complexes by native mass spectrometry.

  2020cites this paper
• Mass spectrometry for semi-experimental protein structure determination and modeling

  2020cites this paper
• Structural predictions of the functions of membrane proteins from HDX-MS

  2020cites this paper
• Interrogating Membrane Protein Structure and Lipid Interactions by Native Mass Spectrometry.

  2020cites this paper
• Mass spectrometry of membrane protein complexes

  2019cites this paper
• Prediction of Protein-Protein Interactions: Looking Through the Kaleidoscope

  2019cites this paper
• Structural mass spectrometry goes viral.

  2019cites this paper
• Predicting Protein Complex Structure from Surface-Induced Dissociation Mass Spectrometry Data

  2019cites this paper
• A Simple Cross-Linking/Mass Spectrometry Workflow to Study System-Wide Protein Interactions

  2019cites this paper
• Ion Mobility in Structural Biology

  2019cites this paper
• Rapid Mapping of Protein Interactions Using Tag‐Transfer Photocrosslinkers

  2018cites this paper
• Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry

  2018cites this paper
• Lipids Shape the Electron Acceptor-Binding Site of the Peripheral Membrane Protein Dihydroorotate Dehydrogenase

  2018cites this paper
• Combining Chemical Cross-linking and Mass Spectrometry of Intact Protein Complexes to Study the Architecture of Multi-subunit Protein Assemblies

  2017cites this paper