High-Ratio Partial Proteolysis with Carrier Proteome (HOLSER) Enables Global Structure Profiling and Site-Resolved Elucidation of Ligand–Protein Interactions

Xuepei Zhang, Hassan Gharibi, Bohdana Sokolova, Zhaowei Meng, Hezheng Lyu, Amir Ata Saei, Massimiliano Gaetani, Roman A. Zubarev · 2026

Read High-Ratio Partial Proteolysis with Carrier Proteome (HOLSER) Enables Global Structure Profiling and Site-Resolved Elucidation of Ligand–Protein Interactions by Xuepei Zhang, Hassan Gharibi, Bohdana Sokolova, Zhaowei Meng, Hezheng Lyu, Amir Ata Saei, Massimiliano Gaetani, Roman A. Zubarev (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/PMC13492042.txt.

Description

Zhang and colleagues in Sweden set out in 2026 a lab method, named HOLSER, to map where drugs grip proteins across a whole cell. Older tricks that nick proteins with enzymes and weigh the bits can spot grip sites, but they read few proteins and wobble from run to run. HOLSER pairs a long, slow nick step with a carrier set of fully cut proteins, spiked in to boost weak signals. Tags let many samples ride in one mass scan.

The team proved the method on three scales. It pinned grip sites for kinase drugs. It also charted shape shifts in the FKBP and mTOR pair when rapamycin was added. And it profiled shapes across the full protein set. Depth and steadiness both beat the older nick methods. The authors offer HOLSER as a sharper lens on how drugs act and where else they may touch.

Catalog record

CREATORXuepei Zhang, Hassan Gharibi, Bohdana Sokolova, Zhaowei Meng, Hezheng Lyu, Amir Ata Saei, Massimiliano Gaetani, Roman A. Zubarev
YEAR2026
COLLECTIONPAPERS
FORMATTXT
FILE SIZE32 KB
LICENSEhttps://creativecommons.org/licenses/by/4.0
RIGHTSCC BY
SOURCEEurope PMC

Source: https://europepmc.org/article/MED/PMC13492042

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