New developments in protein structure–function analysis by MS and use of hydrogen–deuterium exchange microfluidics

The study of protein structure and function has evolved to become a leading discipline in the biophysical sciences. Although it is not yet possible to determine 3D protein structures from MS data alone, multiple MS‐based techniques can be combined to obtain structural and functional data that are complementary to classical protein structure information obtained from NMR or X‐ray crystallography. Monitoring gas‐phase interactions of noncovalent complexes yields information on binding constants, complex stability, and the nature of interactions. Ion mobility MS and chemical crosslinking strategies can be applied to probe the architecture of macromolecular assemblies and protein–ligand complexes. MS analysis of hydrogen–deuterium exchange can be used to determine the localization of secondary structure elements, binding sites and conformational dynamics of proteins in solution. This minireview focuses first on new strategies that combine these techniques to gain insights into protein structure and function. Using one such strategy, we then demonstrate how a novel hydrogen–deuterium exchange microfluidics tool can be used online with an ESI mass spectrometer to monitor regional accessibility in a peptide, as exemplified with amyloid‐β peptide 1–40.

[1]  J. Johansson,et al.  A Membrane Cell for On-line Hydrogen/Deuterium Exchange to Study Protein Folding and Protein-Protein Interactions by Mass Spectrometry* , 2011, Molecular & Cellular Proteomics.

[2]  Thomas Scheibel,et al.  pH-dependent dimerization and salt-dependent stabilization of the N-terminal domain of spider dragline silk--implications for fiber formation. , 2011, Angewandte Chemie.

[3]  M. Tollinger,et al.  Electrostatic Stabilization of a Native Protein Structure in the Gas Phase** , 2010, Angewandte Chemie.

[4]  Tomas Bergman,et al.  A pH-dependent dimer lock in spider silk protein. , 2010, Journal of molecular biology.

[5]  Friedrich Förster,et al.  Structure of the 26S proteasome from Schizosaccharomyces pombe at subnanometer resolution , 2010, Proceedings of the National Academy of Sciences.

[6]  Carol V. Robinson,et al.  Separating and visualising protein assemblies by means of preparative mass spectrometry and microscopy. , 2010, Journal of structural biology.

[7]  Michael G. Sehorn,et al.  Spidroin N-terminal Domain Promotes a pH-dependent Association of Silk Proteins during Self-assembly* , 2010, The Journal of Biological Chemistry.

[8]  M. Przybylski,et al.  On-line bioaffinity-electrospray mass spectrometry for simultaneous detection, identification, and quantification of protein-ligand interactions , 2010, Journal of the American Society for Mass Spectrometry.

[9]  Daniel Barsky,et al.  Integrating Ion Mobility Mass Spectrometry with Molecular Modelling to Determine the Architecture of Multiprotein Complexes , 2010, PloS one.

[10]  J. Klassen,et al.  Quantifying labile protein—Ligand interactions using electrospray ionization mass spectrometry , 2010, Journal of the American Society for Mass Spectrometry.

[11]  R. Houk,et al.  Effects of ion/ion proton transfer reactions on conformation of gas-phase cytochrome c ions , 2010, Journal of the American Society for Mass Spectrometry.

[12]  A. Sali,et al.  Toward an Integrated Structural Model of the 26S Proteasome* , 2010, Molecular & Cellular Proteomics.

[13]  Anna Rising,et al.  Self-assembly of spider silk proteins is controlled by a pH-sensitive relay , 2010, Nature.

[14]  R. Aebersold,et al.  Probing Native Protein Structures by Chemical Cross-linking, Mass Spectrometry, and Bioinformatics , 2010, Molecular & Cellular Proteomics.

[15]  Derek J. Wilson,et al.  A microfluidic reactor for rapid, low-pressure proteolysis with on-chip electrospray ionization. , 2010, Rapid communications in mass spectrometry : RCM.

[16]  L. Kay,et al.  Quaternary dynamics and plasticity underlie small heat shock protein chaperone function , 2010, Proceedings of the National Academy of Sciences.

[17]  E. van Duijn.  Current limitations in native mass spectrometry based structural biology. , 2010, Journal of the American Society for Mass Spectrometry.

[18]  J. Johansson,et al.  Peptide-binding specificity of the prosurfactant protein C Brichos domain analyzed by electrospray ionization mass spectrometry. , 2009, Rapid communications in mass spectrometry : RCM.

[19]  Christopher R. Morgan,et al.  Investigating Solution‐Phase Protein Structure and Dynamics by Hydrogen Exchange Mass Spectrometry , 2009, Current protocols in protein science.

[20]  P. Schnier,et al.  Hydrophobic protein-ligand interactions preserved in the gas phase. , 2009, Journal of the American Chemical Society.

[21]  Christoph H Borchers,et al.  Hydrogen/deuterium exchange mass spectrometry with top-down electron capture dissociation for characterizing structural transitions of a 17 kDa protein. , 2009, Journal of the American Chemical Society.

[22]  Ole N Jensen,et al.  Protein hydrogen exchange measured at single-residue resolution by electron transfer dissociation mass spectrometry. , 2009, Analytical chemistry.

[23]  C. Maier,et al.  Hydrogen/deuterium exchange mass spectrometry. , 2009, Methods in molecular biology.

[24]  Fred W. McLafferty,et al.  Stepwise evolution of protein native structure with electrospray into the gas phase, 10−12 to 102 s , 2008, Proceedings of the National Academy of Sciences.

[25]  Ron Elber,et al.  Early Structural Evolution of Native Cytochrome c after Solvent Removal , 2008, Chembiochem : a European journal of chemical biology.

[26]  Lukas N. Mueller,et al.  Corrigendum: Identification of cross-linked peptides from large sequence databases , 2008, Nature Methods.

[27]  Ruedi Aebersold,et al.  Identification of cross-linked peptides from large sequence databases , 2008, Nature Methods.

[28]  K. Rand,et al.  Development of a peptide probe for the occurrence of hydrogen (1H/2H) scrambling upon gas-phase fragmentation. , 2007, Analytical chemistry.

[29]  H. Jörnvall,et al.  Microfluidic electrocapture interfaced with electrospray mass spectrometry , 2007 .

[30]  S. Englander.  Hydrogen exchange and mass spectrometry: A historical perspective , 2006, Journal of the American Society for Mass Spectrometry.

[31]  Scott A. Busby,et al.  Probing protein ligand interactions by automated hydrogen/deuterium exchange mass spectrometry. , 2006, Analytical chemistry.

[32]  C. Robinson,et al.  Evidence for Macromolecular Protein Rings in the Absence of Bulk Water , 2005, Science.

[33]  Tomas Bergman,et al.  Microfluidic electrocapture for separation of peptides. , 2005, Analytical chemistry.

[34]  D. Clemmer,et al.  Evidence for unfolding and refolding of gas-phase cytochrome c ions in a Paul trap , 2005, Journal of the American Society for Mass Spectrometry.

[35]  H. Jörnvall,et al.  Multistep microreactions with proteins using electrocapture technology. , 2004, Analytical chemistry.

[36]  Renato Zenobi,et al.  Quantitative determination of noncovalent binding interactions using soft ionization mass spectrometry , 2002 .

[37]  R. Wetzel,et al.  Abeta amyloid fibrils possess a core structure highly resistant to hydrogen exchange. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[38]  J. Loo,et al.  Studying noncovalent protein complexes by electrospray ionization mass spectrometry. , 1997, Mass spectrometry reviews.

[39]  B. Ganem,et al.  Detection of noncovalent receptor-ligand complexes by mass spectrometry , 1991 .

[40]  V. Katta,et al.  Conformational changes in proteins probed by hydrogen-exchange electrospray-ionization mass spectrometry. , 1991, Rapid communications in mass spectrometry : RCM.

[41]  M. Mann,et al.  Electrospray ionization for mass spectrometry of large biomolecules. , 1989, Science.