[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Borrego-Diaz, Emma
Kerff, Frédéric ; Boston Biomedical Research Institute > Dominguez Lab
Lee, Sung Haeng
Ferron, Francois
Li, Yu
Dominguez, Roberto
Language :
English
Title :
Crystal structure of the actin-binding domain of alpha-actinin 1: evaluating two competing actin-binding models.
Publication date :
2006
Journal title :
Journal of Structural Biology
ISSN :
1047-8477
eISSN :
1095-8657
Publisher :
Academic Press, San Diego, United States - California
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