Crystal structure of the actin-binding domain of alpha-actinin 1: Evaluating two competing actin-binding models
ABSTRACT 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.
[Show abstract] [Hide abstract]
ABSTRACT: The article provides a theoretical opinion on the relationship of genome and morphology, and suggests biological phenomenon is an activity of information from genome to morphology and function, while the reverse progress is also possible. Therefore, human can reconstruct the full genome of extinct animals from their morphology, and regenerate living animals.
Journal of Muscle Research and Cell Motility 08/2012; 270(33):235-289. · 1.93 Impact Factor