title: Conservation of the regulated structure of folded myosin 2 in species separated by at least 600 million years of independent evolution.
abstract: The myosin 2 family of molecular motors includes isoforms regulated in different ways. Vertebrate smooth-muscle myosin is activated by phosphorylation of the regulatory light chain, whereas scallop striated adductor-muscle myosin is activated by direct calcium binding to its essential light chain. The paired heads of inhibited molecules from myosins regulated by phosphorylation have an asymmetric arrangement with motor-motor interactions. It was unknown whether such interactions were a common motif for inactivation used in other forms of myosin-linked regulation. Using electron microscopy and single-particle image processing, we show that indistinguishable structures are indeed found in myosins and heavy meromyosins isolated from scallop striated adductor muscle and turkey gizzard smooth muscle. The similarities extend beyond the shapes of the heads and interactions between them: In both myosins, the tail folds into three segments, apparently at identical sites; all three segments are in close association outside the head region; and two segments are associated in the same way with one head in the asymmetric arrangement. Thus, these organisms, which have different regulatory mechanisms and diverged from a common ancestor >600 Myr ago, have the same quaternary structure. Conservation across such a large evolutionary distance suggests that this conformation is of fundamental functional importance.
authors.affiliation: Institute of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: Hyun Suk
authors.initials: HS
authors.lastname: Jung
authors.forename: Stan A
authors.initials: SA
authors.lastname: Burgess
authors.forename: Neil
authors.initials: N
authors.lastname: Billington
authors.forename: Melanie
authors.initials: M
authors.lastname: Colegrave
authors.forename: Hitesh
authors.initials: H
authors.lastname: Patel
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Chalovich
authors.forename: Peter D
authors.initials: PD
authors.lastname: Chantler
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Knight
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D008854:Microscopy, Electron; D009130:Muscle, Smooth / Q000648:ultrastructure; D054792:Muscle, Striated / Q000648:ultrastructure; D024462:Myosin Type II / Q000037:antagonists & inhibitors / Q000737:chemistry*; D049910:Pecten; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D014422:Turkeys
chemical_list: D024462:Myosin Type II