2DFS

3-D structure of Myosin-V inhibited state

Summary for 2DFS

• Entry DOI: 10.2210/pdb2dfs/pdb
• EMDB information: 1201
• Descriptor: Myosin-5A, Calmodulin (2 entities in total)
• Functional Keywords: myosin-v, inhibited state, calmodulin, cryoelectron tomography, contractile protein-transport protein complex, contractile protein/transport protein
• Biological source: Gallus gallus (chicken); More
• Total number of polymer chains: 14
• Total formula weight: 453487.59

Authors

Liu, J.,Taylor, D.W.,Krementsova, E.B.,Trybus, K.M.,Taylor, K.A. (deposition date: 2006-03-03, release date: 2006-04-25, Last modification date: 2024-03-13)

Primary citation

Liu, J.,Taylor, D.W.,Krementsova, E.B.,Trybus, K.M.,Taylor, K.A.
Three-dimensional structure of the myosin V inhibited state by cryoelectron tomography
Nature, 442:208-211, 2006

PubMed Abstract: Unconventional myosin V (myoV) is an actin-based molecular motor that has a key function in organelle and mRNA transport, as well as in membrane trafficking. MyoV was the first member of the myosin superfamily shown to be processive, meaning that a single motor protein can 'walk' hand-over-hand along an actin filament for many steps before detaching. Full-length myoV has a low actin-activated MgATPase activity at low [Ca2+], whereas expressed constructs lacking the cargo-binding domain have a high activity regardless of [Ca2+] (refs 5-7). Hydrodynamic data and electron micrographs indicate that the active state is extended, whereas the inactive state is compact. Here we show the first three-dimensional structure of the myoV inactive state. Each myoV molecule consists of two heads that contain an amino-terminal motor domain followed by a lever arm that binds six calmodulins. The heads are followed by a coiled-coil dimerization domain (S2) and a carboxy-terminal globular cargo-binding domain. In the inactive structure, bending of myoV at the head-S2 junction places the cargo-binding domain near the motor domain's ATP-binding pocket, indicating that ATPase inhibition might occur through decreased rates of nucleotide exchange. The actin-binding interfaces are unobstructed, and the lever arm is oriented in a position typical of strong actin-binding states. This structure indicates that motor recycling after cargo delivery might occur through transport on actively treadmilling actin filaments rather than by diffusion.

PubMed: 16625208
DOI: 10.1038/nature04719

Experimental method

ELECTRON CRYSTALLOGRAPHY (24 Å)