Jun Liu / Dianne W Taylor / Elena B Krementsova / Kathleen M Trybus / Kenneth A Taylor /
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 ...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.
EMDB-1201: Three-dimensional structure of the myosin V inhibited state by cryoelectron tomography. PDB-2dfs: 3-D structure of Myosin-V inhibited state Method: EM (subtomogram averaging) / Resolution: 24.0 Å
Source
mus musculus (house mouse)
gallus gallus (chicken)
Keywords
CONTRACTILE PROTEIN/TRANSPORT PROTEIN / myosin-V / inhibited state / calmodulin / cryoelectron tomography / CONTRACTILE PROTEIN-TRANSPORT PROTEIN COMPLEX
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