Inside every cell, proteins act as switches that start and stop the shipping of cargo from one place to another. Biologists know many of the switches but not all the hands that flip them, and finding those partners by trial and error in the lab is slow.
The clever bit
Ryan Vignogna and J. Christopher Fromme at Cornell used AlphaFold-based computer screens to predict which proteins might pair up with Arf1, a switch protein that directs cargo inside cells. That turned a huge search into a short list of candidates worth testing at the bench.
Lab experiments confirmed that Avl9, a protein known to be involved in secretion and cell migration but whose job had never been pinned down, switches Arf1 off. The same activity shows up in the human version. The team also found that a related protein, DENND6A, switches off another target, and proposed that other DENN-domain proteins may work the same way. Avl9 is pulled onto tiny secretory bubbles called vesicles by another switch protein, Rab8, and its switching activity helps cells move.
Hooray
A computer short list led straight to a new job for a little-studied protein and hints at a whole family of similar switches. That gives cell biologists fresh leads to chase. The team calls the group a family of DENN GAP proteins, and it may help explain jobs that other well-known proteins have been doing all along.
What comes next
This is basic cell biology. There's no treatment in it, and it shouldn't be read as a cancer off-switch. The paper was published online in the Journal of Cell Biology on September 9. Many of the candidate proteins named in the paper still have to be tested one by one.