Work

Native Top-Down Mass Spectrometry Links Structure and Gas-Phase Stability of ERα-LBD

Year: 2026

Type: article

Abstract: Defining how protein assemblies form and dissociate is central to understanding biomolecular function. The ligand binding domain (LBD) of estrogen receptor α (ER) forms obligate head-to-head homodimers in solution. The high-affinity leucine zipper that comprises this dimerization interface hinders our ability to measure the kinetics and energetics of oligomer formation. Here, native top-down mass spectrometry (nTDMS) reveals a predominant dimeric ER-LBD assembly under ligand-free conditions. Controlled desolvation voltage drives energy-dependent disassembly to a monomer, enabling the assessment of dimer stability in the gas phase and dissociation pathways. Top-down fragmentation of both dimeric and monomeric species provides sequence-level characterization while preserving assembly context. These results establish nTDMS as a unified approach to link the structure and gas-phase stability of protein assemblies.

Source: Journal of the American Society for Mass Spectrometry

DOI: 10.1021/jasms.6c00287

Authors: Kanchan Pathak, Emma C. Fink, Delaynie Brinkman, Kendall W. Nettles, Sean W. Fanning, Fabio P. Gomes

Institutions: Virginia Commonwealth University, Loyola University Chicago, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology

Language: English

Topic: Mass Spectrometry Techniques and Applications

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: U.S. Department of Defense, Oak Ridge Associated Universities, National Cancer Institute

Awards: G524655853, G9001171509, G9001172323, G9001173988