The importance of the structure-function relationship of proteins and protein-complexes motivates the direct measurement of protein structure in the gas phase by mass spectrometry. This method, termed native mass spectrometry or native electrospray ionization, allows the study of intact complexes and the determination of stoichiometry. The native proteins and complexes can also be investigated by a variety of activation methods to determine structural information. These methods include collisionally activated dissociation (CAD), electron capture/transfer dissociation (ECD/ETD), and infrared multi- photon dissociation (IRMPD). Among the systems we will interrogate using these methods are: (1) Lipoprotein complexes, such as high-density lipoproteins (HDLs) whose heterogeneity is of interest. HDL is an important indicator of cardiovascular health. (2) Membrane-embedded proteins play key roles in cell biology and are pharmaceutical targets (e.g., in anesthesia). (3) Proteins with flexible regions are often actively involved in function and interfacing to other proteins. (4) The stoichiometry of very large protein assemblies is among the first information needed to understand system function and it is still very difficult to get for large complexes. (5) Crosslinking studies provide distance constraints and aid in modeling the geometries of large complexes.

Public Health Relevance

-Public Health Relevance. The Washington University Biomedical Mass Spectrometry Resource has a longstanding history as an active and productive citizen in the NIH Biotechnology Research Resources community. We propose to extend our mission by advancing mass spectrometry technology, development, and research, applying these discoveries to answer critical biomedical research questions, and training the next generation of researchers, towards the ultimate goal of improving public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM103422-40
Application #
9199435
Study Section
Special Emphasis Panel (ZRG1-IMST-B)
Project Start
Project End
Budget Start
2017-01-01
Budget End
2017-12-31
Support Year
40
Fiscal Year
2017
Total Cost
$357,230
Indirect Cost
$122,981
Name
Washington University
Department
Type
Domestic Higher Education
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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