Biomedical Engineering Reference
In-Depth Information
x-ray crystal structures, contrasted with data from electron microscopy ex-
periments showing a large, concerted change between the ADP
·
Pi-bound state
and the ADP state of myosin on actin [18, 19].
Figure 5.1.
Two structures of scallop myosin (left) and human kinesin (right),
showing different structural conformations of the same motor in the same nucleotide
state. PDB accession numbers: 1B7T, scallop myosin ADP structure with lever arm
almost parallel to actin (lighter) [20], 1S5G, scallop myosin ADP structure with
lever arm
∼
45
◦
to actin (darker) [21], 1BG2, human kinesin with disordered neck
linker (lighter) [22], 1MKJ, human kinesin with docked neck linker [23].
Recent Structures: A Breakthrough Interpretation
More recently, structures of smooth myosin and scallop myosin revealed lever
arm conformations that were at 90
◦
[24] and almost parallel to the actin fila-
ment [20]. Referencing the available crystallography, crosslinking, and electron
microscopy data, the lever arm positions of these two structures were inter-
preted as a pre-powerstroke state and an actin-detached state, respectively.
Transitions from the actin-detached conformation to the pre-powerstroke con-
formation and finally to the rigor conformation, would result in movement to
the barbed (plus) end of actin. At the time, it seemed odd that the nucleotides
present in the structures did not correspond to the structural conformations
of myosin for those nucleotide states. ADP was present in the actin-detached
structure, which the authors interpreted to be a weak-binding ATP-like state.
Unlike other structures, the SH2 helix was melted into a conformation con-
sistent with the observed crosslinking results on myosin in the absence of
actin. A recent study has shown that ADP
·
BeFx (ADP
·
beryllium fluoride),
