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Crystal structure of the actin-binding domain of alpha-actinin 1: evaluating two competing actin-binding models.

Publication Date
  • Actinin/Chemistry/Genetics/Metabolism
  • Actins/Chemistry/Metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallography
  • X-Ray/Methods
  • Humans
  • Mice
  • Models
  • Biological
  • Models
  • Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure
  • Secondary
  • Protein Structure
  • Tertiary
  • Rats
  • Sequence Homology
  • Amino Acid
  • Life Sciences :: Biochemistry
  • Biophysics & Molecular Biology [F05]
  • Sciences Du Vivant :: Biochimie
  • Biophysique & Biologie Moléculaire [F05]
  • Biology


Alpha-actinin belongs to the spectrin family of actin crosslinking and bundling proteins that function as key regulators of cell motility, morphology and adhesion. The actin-binding domain (ABD) of these proteins consists of two consecutive calponin homology (CH) domains. Electron microscopy studies on ABDs appear to support two competing actin-binding models, extended and compact, whereas the crystal structures typically display a compact conformation. We have determined the 1.7A resolution structure of the ABD of alpha-actinin 1, a ubiquitously expressed isoform. The structure displays the classical compact conformation. We evaluated the two binding models by surface conservation analysis. The results show a conserved surface that spans both domains and corresponds to two previously identified actin-binding sites (ABS2 and ABS3). A third, and probably less important site, ABS1, is mostly buried in the compact conformation. However, a thorough examination of existing structures suggests a weak and semi-polar binding interface between the two CHs, leaving open the possibility of domain reorientation or opening. Our results are consistent with a two-step binding mechanism in which the ABD interacts first in the compact form observed in the structures, and then transitions toward a higher affinity state, possibly through minor rearrangement of the domains.

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