Accepting the complexity: advance in denaturing top-down proteomics in complex biological systems

Abstract

Proteins act as central players in molecular events and are subject to variations at the DNA, RNA and PTM levels. These variations result in highly complex and dynamic proteoforms that form the human proteome. Since the traditional bottom-up approach suffers from 'peptide-to-protein inference' problem, proteoforms are studied with the top-down technique which analyses intact proteins. Comprehensive information obtained from proteoform level top-down proteomics addresses clinically relevant research questions. Here we reviewed current technical limitations of top-down proteomics and recent solution to address them with emphasis on top-down application in a complex biological context.