Thursday February 28, 2013
“A hybrid approach to studying the structure and mechanism of the motor protein dynein”
Gira Bhabha, Ron Vale Lab, UCSF
Motor proteins play critical roles in intracellular transport and motility, which are required for many cellular functions, including mitosis. Dyneins are large microtubule-based negative-end directed motor proteins that belong to the AAA (ATPases Associated with diverse cellular Activities) family of proteins. Dynein dysfunction is linked to several pathologies including neurodegenerative diseases and cancers. The molecular mechanism of dynein remains obscure, in part due to the challenge posed by its large size and inherent flexibility. We are using a combination of methods, including structural biology, microscopy and bioinformatics to better understand dynein evolution, structure and mechanism. Single-particle electron microscopy and x-ray crystallography have provided structural snapshots of the yeast cytoplasmic dynein motor domain in different nucleotide-bound states, leading to testable hypotheses of how the motor might function. Complementary to the “snapshots” from EM and crystallography, super-resolution 2-color single molecule microscopy allows us to directly probe the dynamics of dynein in solution.