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

Authors

  • Michael Landreh,

    1.  Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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  • Juan Astorga-Wells,

    1.  Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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  • Jan Johansson,

    1.  Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden
    2.  NVS Department, KI-Alzheimer’s Disease Research Center, Karolinska Institutet, Stockholm, Sweden
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  • Tomas Bergman,

    1.  Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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  • Hans Jörnvall

    1.  Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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H. Jörnvall, Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden
Fax: +46 8 33 74 62
Tel: +46 8 524 87702
E-mail: Hans.Jornvall@ki.se

Abstract

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.

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