Proteoform Thursday: Boris Krichel presents: “From Native Complexes to Proteoform Maps: Multi-Dimensional MS Workflows for Kinase Drug Targets”
May 21, 2026 11:00 AM in Eastern Time (US and Canada)
Understanding how kinase activity is regulated requires tracking not just which sites are phosphorylated, but how modification patterns evolve together over time. We addressed this challenge for AMP-activated protein kinase (AMPK), a central metabolic regulator and drug target, by integrating complementary mass spectrometry workflows spanning RPLC-MS intact protein analysis, bottom-up phosphoproteomics, native MS of intact complexes, and top-down sequencing, combining time-resolved kinetic measurements with proteoform-level resolution. This multi-dimensional approach revealed hierarchical phosphorylation cascades, combinatorial proteoform co-occurrence patterns, and regulatory mechanisms invisible to any single method. Our findings demonstrate how hybrid MS strategies can decode the full proteoform architecture of a therapeutically relevant kinase complex.