tailieunhanh - Báo cáo khoa hoc : 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 lead-ing 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. | fFEBS Journal REVIEW ARTICLE New developments in protein structure-function analysis by MS and use of hydrogen-deuterium exchange microfluidics Michael Landreh1 Juan Astorga-Wells1 Jan Johansson2 3 Tomas Bergman1 and Hans Jornvall1 1 Division of PhysiologicalChemistry I Department of MedicalBiochemistry and Biophysics Karolinska Institutet Stockholm Sweden 2 Department of Anatomy Physiology and Biochemistry Swedish University of AgriculturalSciences Uppsala Sweden 3 NVS Department KI-Alzheimer s Disease Research Center Karolinska Institutet Stockholm Sweden Keywords deuterium exchange ESI-MS gas-phase interaction ion mobility protein structure Correspondence H. Jornvall 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 Received 11 April 2011 revised 1 June 2011 accepted 8 June 2011 doi 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 non-covalent 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 hydro-gen-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. .