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Coarse‐grained modeling of conformational transitions underlying the processive stepping of myosin V dimer along filamentous actin
Author(s) -
Zheng Wenjun
Publication year - 2011
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.23055
Subject(s) - adenosine diphosphate , myosin , biophysics , dimer , actin , myosin head , adenosine triphosphate , processivity , chemistry , nucleotide , conformational change , stereochemistry , myosin light chain kinase , biochemistry , enzyme , biology , polymerase , platelet , platelet aggregation , organic chemistry , gene , immunology
Abstract To explore the structural basis of processive stepping of myosin V along filamentous actin, we have performed comprehensive modeling of its key conformational states and transitions with an unprecedented residue level of details. We have built structural models for a myosin V monomer complexed with filamentous actin at four biochemical states [adenosine diphosphate (ATP)‐, adenosine diphosphate (ADP)‐phosphate‐, ADP‐bound or nucleotide‐free]. Then we have modeled a myosin V dimer (consisting of lead and rear head) at various two‐head‐bound states with nearly straight lever arms rotated by intramolecular strain. Next, we have performed transition pathway modeling to determine the most favorable sequence of transitions (namely, phosphate release at the lead head followed by ADP release at the rear head, while ADP release at the lead head is inhibited), which underlie the kinetic coordination between the two heads. Finally, we have used transition pathway modeling to reveal the order of structural changes during three key biochemical transitions (phosphate release at the lead head, ADP release and ATP binding at the rear head), which shed lights on the strain‐dependence of the allosterically coupled motions at various stages of myosin V's work cycle. Our modeling results are in agreement with and offer structural insights to many results of kinetic, single‐molecule and structural studies of myosin V. Proteins 2011; © 2011 Wiley‐Liss, Inc.