4XA3: Crystal Structure Of The Coiled-coil Surrounding Skip 2 Of Myh7

Citation:
Abstract
The rod of sarcomeric myosins directs thick filament assembly and is characterized by the insertion of four skip residues that introduce discontinuities in the coiled-coil heptad repeats. We report here that the regions surrounding the first three skip residues share high structural similarity despite their low sequence homology. Near each of these skip residues, the coiled-coil transitions to a nonclose-packed structure inducing local relaxation of the superhelical pitch. Moreover, molecular dynamics suggest that these distorted regions can assume different conformationally stable states. In contrast, the last skip residue region constitutes a true molecular hinge, providing C-terminal rod flexibility. Assembly of myosin with mutated skip residues in cardiomyocytes shows that the functional importance of each skip residue is associated with rod position and reveals the unique role of the molecular hinge in promoting myosin antiparallel packing. By defining the biophysical properties of the rod, the structures and molecular dynamic calculations presented here provide insight into thick filament formation, and highlight the structural differences occurring between the coiled-coils of myosin and the stereotypical tropomyosin. In addition to extending our knowledge into the conformational and biological properties of coiled-coil discontinuities, the molecular characterization of the four myosin skip residues also provides a guide to modeling the effects of rod mutations causing cardiac and skeletal myopathies.
PDB ID: 4XA3Download
MMDB ID: 130524
PDB Deposition Date: 2014/12/12
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.55  Å
Similar Structures:
Biological Unit for 4XA3: dimeric; determined by author and by software (PISA)
Molecular Components in 4XA3
Label Count Molecule
Proteins (2 molecules)
2
Gp7-myh7(1361-1425)-eb1 Chimera Protein
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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