St. Jude scientists discovered ALK 30 years ago. This target is important in cancers such as pediatric neuroblastoma. How ALK is activated has been unknown until now.
Scientists used structural biology techniques to find the answer. They captured the shape of a part of ALK called the extracellular region. They visualized the ALK extracellular region alone and when bound to ligand. Ligands are molecules that bind to proteins to carry out a function.
ALK is activated when the ligands ALKAL1 and ALKAL2 bind to its extracellular regions. The team showed that the ligands pin ALK to the cell membrane. This is a unique method of activation.
“Knowing the mechanism and having the structure showing how ligands activate ALK will present new therapeutic opportunities,” said Charalampos Babis Kalodimos, PhD, Structural Biology chair.
Nature published this work.