Conformational insight into multi-protein signaling assemblies by hydrogen-deuterium exchange mass spectrometry.

Hydrogen-deuterium exchange (HDX) mass spectrometry (MS) can provide information about proteins that can be challenging to obtain by other means. Structure/function relationships, binding interactions, and the effects of modification have all been measured with HDX MS for a diverse and growing array of signaling proteins and multiprotein signaling complexes. As a result of hardware and software improvements, receptors and complexes involved in cellular signaling-including those associated with membranes-can now be studied. The growing body of HDX MS studies of signaling complexes at membranes is particularly exciting. Recent examples are presented to illustrate what can be learned about signaling proteins with this technique.

[1]  Piotr Sliz,et al.  Conformational locking upon cooperative assembly of notch transcription complexes. , 2012, Structure.

[2]  K. Chung,et al.  Different conformational dynamics of various active states of β-arrestin1 analyzed by hydrogen/deuterium exchange mass spectrometry. , 2015, Journal of structural biology.

[3]  J. Jorgenson,et al.  A Conformational Investigation of Propeptide Binding to the Integral Membrane Protein γ-Glutamyl Carboxylase Using Nanodisc Hydrogen Exchange Mass Spectrometry , 2014, Biochemistry.

[4]  John R Engen,et al.  Analytical Aspects of Hydrogen Exchange Mass Spectrometry. , 2015, Annual review of analytical chemistry.

[5]  J. Qian,et al.  Visualization of arrestin recruitment by a G Protein-Coupled Receptor , 2014, Nature.

[6]  J. Burke,et al.  Probing the dynamic regulation of peripheral membrane proteins using hydrogen deuterium exchange-MS (HDX-MS). , 2015, Biochemical Society transactions.

[7]  J. Jorgenson,et al.  Conformational Transitions in the Membrane Scaffold Protein of Phospholipid Bilayer Nanodiscs* , 2011, Molecular & Cellular Proteomics.

[8]  B. Lillemeier,et al.  T cell receptor dwell times control the kinase activity of Zap70 , 2015, Nature Immunology.

[9]  Lars Konermann,et al.  Mass spectrometry methods for studying structure and dynamics of biological macromolecules. , 2014, Analytical chemistry.

[10]  Roger L. Williams,et al.  The intrinsically disordered tails of PTEN and PTEN-L have distinct roles in regulating substrate specificity and membrane activity , 2015, The Biochemical journal.

[11]  Carol V Robinson,et al.  Mass spectrometry of protein complexes: from origins to applications. , 2015, Annual review of physical chemistry.

[12]  M. J. Chalmers,et al.  Protein conformation ensembles monitored by HDX reveal a structural rationale for abscisic acid signaling protein affinities and activities. , 2013, Structure.

[13]  Jan Steyaert,et al.  Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes , 2015, Science.

[14]  S. Radford,et al.  Mass spectrometric methods to analyze the structural organization of macromolecular complexes. , 2015, Methods.

[15]  J. Jorgenson,et al.  Conformational analysis of membrane proteins in phospholipid bilayer nanodiscs by hydrogen exchange mass spectrometry. , 2010, Analytical chemistry.

[16]  John R Engen,et al.  Hydrogen Exchange Mass Spectrometry: Are We Out of the Quicksand? , 2012, Journal of The American Society for Mass Spectrometry.

[17]  Roger L. Williams,et al.  G Protein–Coupled Receptor–Mediated Activation of p110β by Gβγ Is Required for Cellular Transformation and Invasiveness , 2012, Science Signaling.

[18]  Briana C. Vernon,et al.  Hydrogen Exchange Mass Spectrometry of Proteins at Langmuir Monolayers. , 2015, Analytical chemistry.

[19]  E. Prossnitz,et al.  Conformational differences between arrestin2 and pre-activated mutants as revealed by hydrogen exchange mass spectrometry. , 2005, Journal of molecular biology.

[20]  E. Reinherz,et al.  Antibody mechanics on a membrane-bound HIV segment essential for GP41-targeted viral neutralization , 2011, Nature Structural &Molecular Biology.

[21]  L. Walensky,et al.  Inhibition of Pro-apoptotic BAX by a noncanonical interaction mechanism. , 2015, Molecular cell.

[22]  Hideaki E. Kato,et al.  Effective Application of Bicelles for Conformational Analysis of G Protein-Coupled Receptors by Hydrogen/Deuterium Exchange Mass Spectrometry , 2015, Journal of The American Society for Mass Spectrometry.

[23]  John R. Engen,et al.  Applications of Hydrogen/Deuterium Exchange MS from 2012 to 2014 , 2014, Analytical chemistry.

[24]  R. Weis,et al.  Hydrogen exchange mass spectrometry of functional membrane-bound chemotaxis receptor complexes. , 2013, Biochemistry.

[25]  P. Griffin,et al.  Integration of G Protein α (Gα) Signaling by the Regulator of G Protein Signaling 14 (RGS14)* , 2015, The Journal of Biological Chemistry.

[26]  Virgil L. Woods,et al.  Conformational changes in the G protein Gs induced by the β2 adrenergic receptor , 2011, Nature.

[27]  K. Chung,et al.  Different conformational dynamics of β-arrestin1 and β-arrestin2 analyzed by hydrogen/deuterium exchange mass spectrometry. , 2015, Biochemical and biophysical research communications.

[28]  M. J. Chalmers,et al.  Ligand-dependent perturbation of the conformational ensemble for the GPCR β2 adrenergic receptor revealed by HDX. , 2011, Structure.

[29]  M. J. Chalmers,et al.  Dynamics of the beta2-adrenergic G-protein coupled receptor revealed by hydrogen-deuterium exchange. , 2010, Analytical chemistry.

[30]  M. Chance,et al.  Conformational dynamics of activation for the pentameric complex of dimeric G protein-coupled receptor and heterotrimeric G protein. , 2012, Structure.

[31]  R. Weis,et al.  Hydrogen Exchange Differences between Chemoreceptor Signaling Complexes Localize to Functionally Important Subdomains , 2014, Biochemistry.

[32]  Roger L. Williams,et al.  Molecular determinants of PI3Kγ-mediated activation downstream of G-protein–coupled receptors (GPCRs) , 2013, Proceedings of the National Academy of Sciences.