A hidden map of 3,000 new signals dictates how proteins enter and leave the control center of human cells.
Traditional methods for finding nuclear export signals relied on looking for specific repeating sequences that often missed the mark. Researchers used AlphaFold 3 to model 4,000 different proteins and found thousands of signals that do not follow any known pattern. These signals act like VIP passes that let proteins pass through the wall of the cell nucleus via the XPO1 transporter. This massive interactome explains how cells coordinate their most basic functions and what goes wrong in diseases like cancer. It provides a complete directory of the cellular traffic that was previously invisible to biologists.
Deep Learning–Based Atlas of the XPO1 Interactome at Proteome Scale
SSRN · 6690581
Exportin 1 (XPO1/CRM1) is the principal nuclear export receptor for cargos bearing hydrophobic nuclear export sequences (NESs). Dysregulation of XPO1-dependent export is implicated in cancer, neurodegeneration, and other diseases, yet a comprehensive view of XPO1 function remains limited by the poor reliability of sequence-based NES prediction. Existing predictors are largely derived from a small set of XPO1-cargo structures and are therefore biased toward canonical docking geometries, limiting