Our cells rely on microscopic highways and specialized protein vehicles to move everything—from positioning organelles to carting protein instructions to disposing of cellular garbage. These highways (called microtubules) and vehicles (called motor proteins) are indispensable to cellular function and survival.

The dysfunction of motor proteins and their associated proteins can lead to severe neurodevelopmental and neurodegenerative disorders. For example, the dysfunction of Lis1, a partner protein to the motor protein dynein, can lead to the rare fatal birth defect lissencephaly, or “smooth brain,” for which there is no cure. But therapeutics that target and restore dynein or Lis1 function could change those dismal outcomes—and developing those therapeutics depends on thoroughly understanding how dynein and Lis1 interact.

New research from the Salk Institute and UC San Diego captured short movies of Lis1 “turning on” dynein. The movies allowed the team to catalog 16 shapes that the two proteins take as they interact, some of which have never been seen before. These insights will be foundational for designing future therapeutics that restore dynein and Lis1 function, since they shine a light on precise locations where drugs could interact with the proteins.