Myosin Subfragment 1 Structures Reveal a Partially Bound Nucleotide and a Complex Salt Bridge That Helps Couple Nucleotide and Actin Binding

Structural studies of myosin have induced 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-Å x-ray structure of the scallop myosin head domain (subfragment 1) in the ADP...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-06, Vol.101 (24), p.8930-8935
Main Authors: Risal, Dipesh, Gourinath, S., Himmel, Daniel M., Szent-Györgyi, Andrew G., Cohen, Carolyn
Format: Article
Language:English
Subjects:
Actins
Actins - metabolism
Adenosine Diphosphate - metabolism
Amino Acids - chemistry
Animals
Arm
Binding Sites
Biochemistry
Biological Sciences
Biophysics
Bridge engineering
Crystal structure
Crystallography, X-Ray
Kinetics
Marine
Models, Molecular
Mollusca - chemistry
Myosin Subfragments - chemistry
Myosin Subfragments - genetics
Myosin Subfragments - metabolism
Nucleotides
Protein Binding
Protein isoforms
Protein Structure, Tertiary
Proteins
Salt
Salts
Skeletal muscle
Static Electricity
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Summary:Structural studies of myosin have induced 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-Å x-ray structure of the scallop myosin head domain (subfragment 1) in the ADP-bound near-rigor state (lever arm ≈45° 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-Å 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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0403002101