# Advancing Mass Spectrometry Analyses of Proteins, Assemblies, and Proteoforms

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $378,080

## Abstract

PROJECT SUMMARY/ABSTRACT
Understanding cellular processes and pathways in depth requires methods that not only investigate the
composition and arrangement of various protein assemblies, but that also elucidate their dynamics and
functional regulation. Experimental strategies delivering structural information beyond primary sequence; i.e.,
higher-order structure and protein modifications, connect proteomics to structural biology in ways yielding
potential insights into complex disease mechanisms. New techniques based on mass spectrometry (MS),
native MS (i.e., measuring biomolecules in their native solution environment preserving ligand- and other
molecular interactions), and top-down MS/proteomics will be advanced and applied to facilitate the
characterization of proteins and protein assemblies. Coupling sensitive ionization, solution- and gas-phase
separations, new electron-based dissociation methods (e.g., electron capture dissociation, ECD; electron
ionization dissociation, EID) and other activation/dissociation techniques to ultra-high resolution mass
spectrometry will provide an experimental platform for complete sequence and proteoform coverage. These
advanced tools will be employed to characterize important biological complexes for which high-resolution
structures have been difficult to obtain, including G-coupled protein receptors (GPCRs) and other membrane
proteins. The exploration of links between post-translational modifications (PTMs) and proteoforms to the
aggregation and toxicity of neurodegenerative diseases such as Alzheimer's disease (AD) will be furthered by
our advanced MS methods. Our experimental strategies apply broadly and integrate with numerous
biophysical techniques to enable the detailed structural study of large and complex molecular machines and to
provide insights into their dynamics. Native top-down MS promises to advance structural biology and to hasten
drug discovery and development. Improvements in MS-based technologies can advance our understanding of
how proteins and protein machines drive biology.

## Key facts

- **NIH application ID:** 10824294
- **Project number:** 5R35GM145286-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Joseph A Loo
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $378,080
- **Award type:** 5
- **Project period:** 2022-07-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10824294

## Citation

> US National Institutes of Health, RePORTER application 10824294, Advancing Mass Spectrometry Analyses of Proteins, Assemblies, and Proteoforms (5R35GM145286-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10824294. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*