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. © 2010 Elsevier Ltd.
Kim, H. J., Hsin, J., Liu, Y., Selvin, P. R., & Schulten, K. (2010). Formation of Salt Bridges Mediates Internal Dimerization of Myosin VI Medial Tail Domain. Structure, 18(11), 1443–1449. https://doi.org/10.1016/j.str.2010.09.011