A conformational transition in the myosin VI converter contributes to the variable step size.
Biophys J
; 101(10): 2436-44, 2011 Nov 16.
Article
in En
| MEDLINE
| ID: mdl-22098742
ABSTRACT
Myosin VI (MVI) is a dimeric molecular motor that translocates backwards on actin filaments with a surprisingly large and variable step size, given its short lever arm. A recent x-ray structure of MVI indicates that the large step size can be explained in part by a novel conformation of the converter subdomain in the prepowerstroke state, in which a 53-residue insert, unique to MVI, reorients the lever arm nearly parallel to the actin filament. To determine whether the existence of the novel converter conformation could contribute to the step-size variability, we used a path-based free-energy simulation tool, the string method, to show that there is a small free-energy difference between the novel converter conformation and the conventional conformation found in other myosins. This result suggests that MVI can bind to actin with the converter in either conformation. Models of MVI/MV chimeric dimers show that the variability in the tilting angle of the lever arm that results from the two converter conformations can lead to step-size variations of â¼12 nm. These variations, in combination with other proposed mechanisms, could explain the experimentally determined step-size variability of â¼25 nm for wild-type MVI. Mutations to test the findings by experiment are suggested.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myosin Heavy Chains
Type of study:
Prognostic_studies
Language:
En
Journal:
Biophys J
Year:
2011
Document type:
Article