Frank Sobott

About

My research is aimed at development and applications of methods based on “native” mass spectrometry and ion mobility and associated structural proteomics and computational techniques, in order to understand and characterize noncovalent interactions in chemistry and biology. I am particularly motivated by understanding structure and dynamics of molecules and complexes of high biochemical and biomedical relevance, in order to provide innovative tools for the development of novel drugs. I am recognized as one of the key, early pioneers of "native MS" and achievements during my career over the last 25 years include: 1) Developed novel method for gentle ionization of supra- and biomolecular complexes which uses liquid jets/droplets in combination with a desorption laser ("LILBID", Anal. Chem., 69 (1997), 3587 and Angew. Chem. Int. Ed., 39 (2000), 3901) 2) First high-mass modified MS for large protein complexes and application to study intact ribosomes (Proc. Natl. Acad. Sci. USA, 102 (2005), 8192) 3) Significant contributions to 27 x-ray structures at Structural Genomics Consortium (PDB; Proc. Natl. Acad. Sci. USA, 103 (2006), 17237) 4) Utilized hydrophobically stabilized detergent micelles and native MS with ion mobility and molecular modelling to characterize conformational transitions of an ion channel (MscL), capturing intermediate opening states 5) Developed top-down protein fragmentation technique which links information on protein higher-order structure (conformation, assembly, ligand binding) with sequence data in one experiment - particularly useful for the characterization of disordered regions 6) Characterized conformational space, binding sites and effects of small molecules on a-synuclein folding and assembly, enabling conformation-sensitive screening of drug candidates even for non-specific binders which modulate amyloid aggregation and toxicity 7) Contributed to fundamental biophysical understanding of protein structural dynamics, determinants of intrinsic disorder and influence of charge on structure (J. Am. Chem. Soc., 137 (2015), 4236 and J. Am. Soc. Mass Spectrom., 28 (2017), 69) 8) Engaged in dissemination of structural proteomics know-how to students, structural biologists and colleagues in biopharma industry, thereby establishing best practice application of these tools to characterize proteins of therapeutic interest (Chair of COST Action, H2020 and Marie-Curie network subject to funding)

Work

University of Leeds

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Chair of Biomolecular Mass Spectrometry

United Kingdom of Great Britain and Northern Ireland

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Publications

Radical solutions: Principles and application of electron-based dissociation in mass spectrometry-based analysis of protein structure

Mass Spectrometry Reviews

journal-article

The effect of reactive oxygen and nitrogen species on the structure of cytoglobin: A potential tumor suppressor

Redox Biology

journal-article

A broader view on ion heating in traveling-wave devices using fragmentation of CsI clusters and extent of H˙ migration as molecular thermometers

The Analyst

journal-article

A broader view on ion heating in traveling-wave devices using fragmentation of CsI clusters and extent of H migration as molecular thermometers

Analyst

journal-article

A homologue of the Parkinson's disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover

Nature Communications

journal-article

Analyzing complex mixtures of drug-like molecules: Ion mobility as an adjunct to existing liquid chromatography-(tandem) mass spectrometry methods

Journal of Chromatography A

journal-article

Antarctic fish versus human cytoglobins – The same but yet so different

Journal of Inorganic Biochemistry

journal-article

Apparent activation energies of protein–protein complex dissociation in the gas–phase determined by electrospray mass spectrometry

Analytical and Bioanalytical Chemistry

journal-article

AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet

Nature Chemical Biology

journal-article

Conformational Space and Stability of ETD Charge Reduction Products of Ubiquitin

Journal of the American Society for Mass Spectrometry

journal-article

Estimation of rates of reactions triggered by electron transfer in top-down mass spectrometry

Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)

book

Hidden States within Disordered Regions of the CcdA Antitoxin Protein

Journal of the American Chemical Society

journal-article

Mechanisms of Peptide Oxidation by Hydroxyl Radicals: Insight at the Molecular Scale

Journal of Physical Chemistry C

journal-article

Native mass spectrometry for the characterization of structure and interactions of membrane proteins

Methods in Molecular Biology

book

Phase Separation of C9orf72 Dipeptide Repeats Perturbs Stress Granule Dynamics

Molecular Cell

journal-article

Preprotein mature domains contain translocase targeting signals that are essential for secretion

Journal of Cell Biology

journal-article

Proton Dynamics in Protein Mass Spectrometry

Journal of Physical Chemistry Letters

journal-article

Raman optical activity of human α-synuclein in intrinsically disordered, micelle-bound α-helical, molten globule and oligomeric β-sheet state

Journal of Raman Spectroscopy

journal-article

Specific sequences in the N-terminal domain of human small heat-shock protein HSPB6 dictate preferential hetero-oligomerization with the orthologue HSPB1

Journal of Biological Chemistry

journal-article

The structural basis for dynamic DNA binding and bridging interactions which condense the bacterial centromere

eLife

journal-article

ATP and autophosphorylation driven conformational changes of HipA kinase revealed by ion mobility and crosslinking mass spectrometry

Analytical and Bioanalytical Chemistry

journal-article

Combining density functional theory (DFT) and collision cross-section (CCS) calculations to analyze the gas-phase behaviour of small molecules and their protonation site isomers

Analyst

journal-article

Covalent adducts of melphalan with free amino acids and a model peptide studied by liquid chromatography/tandem mass spectrometry

Rapid Communications in Mass Spectrometry

journal-article

Development of a novel antibody-tetrazine conjugate for bioorthogonal pretargeting

Organic and Biomolecular Chemistry

journal-article

Gas-phase microsolvation of ubiquitin: Investigation of crown ether complexation sites using ion mobility-mass spectrometry

Analyst

journal-article

Lipids modulate the conformational dynamics of a secondary multidrug transporter

Nature Structural and Molecular Biology

journal-article

Opposite Structural Effects of Epigallocatechin-3-gallate and Dopamine Binding to α-Synuclein

Analytical Chemistry

journal-article

The preferential heterodimerization of human small heat shock proteins HSPB1 and HSPB6 is dictated by the N-terminal domain

Archives of Biochemistry and Biophysics

journal-article

Biophysical studies on interactions and assembly of full-size E3 ubiquitin ligase: Suppressor of cytokine signaling 2 (SOCS2)-elongin Bc-cullin 5-ring box protein 2 (RBX2)

Journal of Biological Chemistry

journal-article

Bouncing off the walls: Excited protein complexes tell their story

Chemistry and Biology

journal-article

Characterization of top-down ETD in a travelling-wave ion guide

Methods

journal-article

Differences in the Elemental Isotope Definition May Lead to Errors in Modern Mass-Spectrometry-Based Proteomics

Analytical Chemistry

journal-article

Electron transfer dissociation provides higher-order structural information of native and partially unfolded protein complexes

Proteomics

journal-article

Extending native mass spectrometry approaches to integral membrane proteins

Biological Chemistry

journal-article

Extensive charge reduction and dissociation of intact protein complexes following electron transfer on a quadrupole-ion mobility-time-of-flight MS

Journal of the American Society for Mass Spectrometry

journal-article

Molecular basis for structural heterogeneity of an intrinsically disordered protein bound to a partner by combined ESI-IM-MS and modeling

Journal of the American Society for Mass Spectrometry

journal-article

Protomers of benzocaine: Solvent and permittivity dependence

Journal of the American Chemical Society

journal-article

Signal loss due to oligomerization in ELISA analysis of amyloid-beta can be recovered by a novel sample pre-treatment method

MethodsX

journal-article

Specific and non-specific interactions of ParB with DNA: Implications for chromosome segregation

Nucleic Acids Research

journal-article

Top-down mass spectrometry of intact membrane protein complexes reveals oligomeric state and sequence information in a single experiment

Protein Science

journal-article

Understanding reaction pathways in top-down ETD by dissecting isotope distributions: A mammoth task

International Journal of Mass Spectrometry

journal-article

ETD allows for native surface mapping of a 150 kDa noncovalent complex on a commercial Q-TWIMS-TOF instrument

Journal of the American Society for Mass Spectrometry

journal-article

Global structural changes of an ion channel during its gating are followed by ion mobility mass spectrometry

Proceedings of the National Academy of Sciences of the United States of America

journal-article

The intrinsically disordered domain of the antitoxin phd chaperones the toxin doc against irreversible inactivation and misfolding

Journal of Biological Chemistry

journal-article

Type III restriction endonucleases are heterotrimeric: Comprising one helicase-nuclease subunit and a dimeric methyltransferase that binds only one specific DNA

Nucleic Acids Research

journal-article

Hfq binding changes the structure of Escherichia coli small noncoding RNAs OxyS and RprA, which are involved in the riboregulation of rpoS

RNA

journal-article

LptA assembles into rod-like oligomers involving disorder-to-order transitions

Journal of the American Society for Mass Spectrometry

journal-article

Native Mass Spectrometry Approaches Using Ion Mobility-Mass Spectrometry

Analyzing Biomolecular Interactions by Mass Spectrometry

book

Native ion mobility-mass spectrometry and related methods in structural biology

Biochimica et Biophysica Acta - Proteins and Proteomics

journal-article

Organization of the BcgI restriction-modification protein for the cleavage of eight phosphodiester bonds in DNA

Nucleic Acids Research

journal-article

Organization of the BcgI restriction-modification protein for the transfer of one methyl group to DNA

Nucleic Acids Research

journal-article

Structural plasticity of histones H3-H4 facilitates their allosteric exchange between RbAp48 and ASF1

Nature Structural and Molecular Biology

journal-article

Travelling wave ion mobility and negative ion fragmentation for the structural determination of N-linked glycans

Electrophoresis

journal-article

Characterization of Vibrio cholerae Hfq provides novel insights into the role of the Hfq C-terminal region

Journal of Molecular Biology

journal-article

Contactin-associated protein-2 antibodies in non-paraneoplastic cerebellar ataxia

Journal of Neurology, Neurosurgery and Psychiatry

journal-article

The low-resolution solution structure of Vibrio cholerae Hfq in complex with Qrr1 sRNA

Nucleic Acids Research

journal-article

Characterization of β2-microglobulin conformational intermediates associated to different fibrillation conditions

Journal of Mass Spectrometry

journal-article

Compaction properties of an intrinsically disordered protein: Sic1 and its kinase-inhibitor domain

Biophysical Journal

journal-article

Ion mobility mass spectrometry for extracting spectra of n-glycans directly from incubation mixtures following glycan release: Application to glycans from engineered glycoforms of intact, folded HIV gp120

Journal of the American Society for Mass Spectrometry

journal-article

Metal and redox selectivity of protoporphyrin binding to the heme chaperone CcmE

Metallomics

journal-article

Application of a proteolysis/mass spectrometry method for investigating the effects of inhibitors on hydroxylase structure

Journal of Medicinal Chemistry

journal-article

Comparison of CID Versus ETD Based MS/MS Fragmentation for the Analysis of Protein Ubiquitination

Journal of the American Society for Mass Spectrometry

journal-article

Quadrupole-time-of-flight mass spectrometer modified for higher-energy dissociation reduces protein assemblies to peptide fragments

Analytical Chemistry

journal-article

Codon optimization can improve expression of human genes in Escherichia coli: A multi-gene study

Protein Expression and Purification

journal-article

Structure of the Human Protein Kinase MPSK1 Reveals an Atypical Activation Loop Architecture

Structure

journal-article

Structural and Functional Characterization of the Human Protein Kinase ASK1

Structure

journal-article

The centaurin γ-1 GTPase-like domain functions as an NTPase

Biochemical Journal

journal-article

Structural basis for protein-protein interactions in the 14-3-3 protein family

Proceedings of the National Academy of Sciences of the United States of America

journal-article

Structure of an Hsp90-Cdc37-Cdk4 Complex

Molecular Cell

journal-article

Tandem Mass Spectrometry Reveals the Quaternary Organization of Macromolecular Assemblies

Chemistry and Biology

journal-article

The co-chaperone p23 arrests the Hsp90 ATPase cycle to trap client proteins

Journal of Molecular Biology

journal-article

Understanding Protein Interactions and Their Representation in the Gas Phase of the Mass Spectrometer

Principles of Mass Spectrometry Applied to Biomolecules

book

Heptameric (L12)6/L10 rather than canonical pentameric complexes are found by tandem MS of intact ribosomes from thermophilic bacteria

Proceedings of the National Academy of Sciences of the United States of America

journal-article

The flight of macromolecular complexes in a mass spectrometer

Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences

journal-article

Biochemical and structural studies of the interaction of Cdc37 with Hsp90

Journal of Molecular Biology

journal-article

Characterising electrosprayed biomolecules using tandem-MS - The noncovalent GroEL chaperonin assembly

International Journal of Mass Spectrometry

journal-article

Tandem Mass Spectrometry Defines the Stoichiometry and Quaternary Structural Arrangement of Tryptophan Molecules in the Multiprotein Complex TRAP

Journal of the American Chemical Society

journal-article

Gas-phase dissociation pathways of a tetrameric protein complex

International Journal of Mass Spectrometry

journal-article

Reactions of gold cluster cations Aun+ (n=1-12) with H2S and H2

Journal of Chemical Physics

journal-article

Thermal dissociation of multimeric protein complexes by using nanoelectrospray mass spectrometry

Analytical Chemistry

journal-article

A high-mass Q-TOF for the analysis of protein complexes

Proceedings 50th ASMS Conference on Mass Spectrometry and Allied Topics

conference-paper

A nano-electrospray investigation into the subunit exchange of small heat shock proteins

Proceedings 50th ASMS Conference on Mass Spectrometry and Allied Topics

conference-paper

A tandem mass spectrometer for improved transmission and analysis of large macromolecular assemblies

Analytical Chemistry

journal-article

Protein complexes gain momentum

Current Opinion in Structural Biology

journal-article

Subunit exchange of multimeric protein complexes: Real-time monitoring of subunit exchange between small heat shock proteins by using electrospray mass spectrometry

Journal of Biological Chemistry

journal-article

Detection of intact hemoglobin from aqueous solution with laser desorption mass spectrometry

Rapid Communications in Mass Spectrometry

journal-article

Speciation in solution: Silicate oligomers in aqueous solutions detected by mass spectrometry

Angewandte Chemie - International Edition

journal-article

Studying noncovalent protein complexes in aqueous solution with laser desorption mass spectrometry

International Journal of Mass Spectrometry

journal-article

Ionic clathrates from aqueous solutions detected with laser induced liquid beam ionization/desorption mass spectrometry

International Journal of Mass Spectrometry

journal-article

Laser desorption mass spectrometry on liquid beams

European Journal of Mass Spectrometry

journal-article

Examination of condensation products of Group 4 alkoxides with laser- induced liquid beam ionization/desorption mass spectrometry

Chemistry - A European Journal

journal-article

Laser desorption mass spectrometry on thin liquid jets

Fresenius' Journal of Analytical Chemistry

journal-article

Cation Selectivity of Natural and Synthetic lonophores Probed with Laser-Induced Liquid Beam Mass Spectrometry

Analytical Chemistry

journal-article