title: Myosin subfragment 1 structures reveal a partially bound nucleotide and a complex salt bridge that helps couple nucleotide and actin binding.
abstract: Structural studies of myosin have indicated some of the conformational changes that occur in this protein during the contractile cycle, and we have now observed a conformational change in a bound nucleotide as well. The 3.1-A x-ray structure of the scallop myosin head domain (subfragment 1) in the ADP-bound near-rigor state (lever arm =45 degrees to the helical actin axis) shows the diphosphate moiety positioned on the surface of the nucleotide-binding pocket, rather than deep within it as had been observed previously. This conformation strongly suggests a specific mode of entry and exit of the nucleotide from the nucleotide-binding pocket through the so-called "front door." In addition, using a variety of scallop structures, including a relatively high-resolution 2.75-A nucleotide-free near-rigor structure, we have identified a conserved complex salt bridge connecting the 50-kDa upper and N-terminal subdomains. This salt bridge is present only in crystal structures of muscle myosin isoforms that exhibit a strong reciprocal relationship (also known as coupling) between actin and nucleotide affinity.
authors.affiliation: Rosenstiel Basic Medical Sciences Research Center, MS 029, Waltham, MA 02454-9110, USA.
authors.forename: Dipesh
authors.initials: D
authors.lastname: Risal
authors.forename: S
authors.initials: S
authors.lastname: Gourinath
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Himmel
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Szent-Györgyi
authors.forename: Carolyn
authors.initials: C
authors.lastname: Cohen
mesh_terms: D000199:Actins / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D007700:Kinetics; D008958:Models, Molecular; D008974:Mollusca / Q000737:chemistry; D015879:Myosin Subfragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D055672:Static Electricity
chemical_list: D000199:Actins; D000596:Amino Acids; D015879:Myosin Subfragments; D000244:Adenosine Diphosphate