Crystallography Research Today is a free monthly online journal that collates and summarizes the latest research about Crystallography, including details on x-ray crystals, techniques, analyses, structures.

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

Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA.

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.

Published 28 August 2006 in J Struct Biol, 155(2): 230-8.
Full-text of this article is available online (may require subscription).

© 2005-2008 Crystallography Research Today. All Rights Reserved.