Reference : Crystal structure of the actin-binding domain of alpha-actinin 1: evaluating two competi...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Crystal structure of the actin-binding domain of alpha-actinin 1: evaluating two competing actin-binding models.
Borrego-Diaz, Emma [> > > >]
Kerff, Frédéric mailto [Boston Biomedical Research Institute > > Dominguez Lab > >]
Lee, Sung Haeng [> > > >]
Ferron, Francois [> > > >]
Li, Yu [> > > >]
Dominguez, Roberto [> > > >]
Journal of Structural Biology
Academic Press
Yes (verified by ORBi)
San Diego
[en] 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
[en] 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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