Publication Abstract from PubMed
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.
Crystal structure of the actin-binding domain of alpha-actinin 1: evaluating two competing actin-binding models.,Borrego-Diaz E, Kerff F, Lee SH, Ferron F, Li Y, Dominguez R J Struct Biol. 2006 Aug;155(2):230-8. Epub 2006 Apr 25. PMID:16698282[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
