title: New developments in protein structure-function analysis by MS and use of hydrogen-deuterium exchange microfluidics.
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.
authors.affiliation: Division of Physiological Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Landreh
authors.forename: Juan
authors.initials: J
authors.lastname: Astorga-Wells
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
authors.forename: Tomas
authors.initials: T
authors.lastname: Bergman
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
mesh_terms: D000818:Animals; D003903:Deuterium / Q000737:chemistry; D041961:Deuterium Exchange Measurement; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D013058:Mass Spectrometry; D044085:Microfluidics; D008958:Models, Molecular; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins; D006859:Hydrogen; D003903:Deuterium