{Reference Type}: Journal Article
{Title}: The mechanism and energetics of the dynein priming stroke.
{Author}: Golcuk M;Yilmaz SZ;Yildiz A;Gur M;
{Journal}: Structure
{Volume}: 32
{Issue}: 5
{Year}: 2024 May 2
{Factor}: 5.871
{DOI}: 10.1016/j.str.2024.02.003
{Abstract}: Dyneins are an AAA+ motor responsible for motility and force generation toward the minus end of microtubules. Dynein motility is powered by nucleotide-dependent transitions of its linker domain, which transitions between straight (post-powerstroke) and bent (pre-powerstroke) conformations. To understand the dynamics and energetics of the linker, we performed all-atom molecular dynamics simulations of human dynein-2 primed for its power stroke. Simulations revealed that the linker can adopt either a bent conformation or a semi-bent conformation, separated by a 5.7 kT energy barrier. The linker cannot switch back to its straight conformation in the pre-powerstroke state due to a steric clash with the AAA+ ring. Simulations also showed that an isolated linker has a free energy minimum near the semi-bent conformation in the absence of the AAA+ ring, indicating that the linker stores energy as it bends and releases this energy during the powerstroke.