Top-down mass spectrometry is a powerful technique for uncovering all proteoforms in a sample. It offers completely unique insights about the presence of PTMs at different positions, unique copies with terminal processing/point mutations, and many others.

Relevant literature:

* Tamara et al; A colorful pallet of B-phycoerythrin proteoforms exposed by a multimodal mass spectrometry approach, Chem, 2019

* Tamara et al; Symmetry of charge partitioning in collisional and UV photon-induced dissociation of protein assemblies, JACS, 2016

* Lössl et al; Deciphering the interplay among multisite phosphorylation, interaction dynamics, and conformational transitions in a tripartite protein system, ACS Central Science, 2016

It works by spraying denatured, intact proteins into the mass spectrometer. Upon isolation and fragmentation the sequence and the PTMs can typically be determined.