Formation of salt bridges mediates internal dimerization of myosin VI medial tail domain.
The unconventional motor protein, myosin VI, is known to dimerize upon cargo binding to its C-terminal end. It has been shown that one of its tail domains, called the medial tail domain, is a dimerization region. The domain contains an unusual pattern of alternating charged residues and a few hydrophobic residues. To reveal the unknown dimerization mechanism of the medial tail domain, we employed molecular dynamics and single-molecule experimental techniques. Both techniques suggest that the formation of electrostatic-based interhelical salt bridges between oppositely charged residues is a key dimerization factor. For the dimerization to occur, the two identical helices within the dimer do not bind in a symmetric fashion, but rather with an offset of about one helical repeat. Calculations of the dimer-dissociation energy find the contribution of hydrophobic residues to the dimerization process to be minor; they also find that the asymmetric homodimer state is energetically favorable over a state of separate helices.
Department of Physics and Center of the Physics of Living Cells, University of Illinois, Urbana, IL 61801, USA.
Hyeongjun
H
Kim
Jen
J
Hsin
Yanxin
Y
Liu
Paul R
PR
Selvin
Klaus
K
Schulten
D019281:Dimerization; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D018995:Myosin Heavy Chains / Q000737:chemistry*; D017434:Protein Structure, Tertiary / Q000235:genetics*; D012492:Salts / Q000737:chemistry*; D055672:Static Electricity
D012492:Salts; C089785:myosin VI; D018995:Myosin Heavy Chains