Utrophin (green) can bind to actin (light blue) in two different modes.
Utrophin, a member of the spectrin superfamily of actin-binding proteins ubiquitously expressed in human cells, helps link the actin cytoskeleton to the extracellular matrix. Galkin et al. report on
page 231 that a newly developed image analysis method identifies two different modes of utrophin binding to F-actin. The findings contradict earlier studies on utrophin–actin interactions and provide a clearer explanation of how relatively few proteins may generate the diverse interactions and structures seen in the actin cytoskeleton.The amino-terminal domain of utrophin contains a tandem pair of calponin homology (CH) domains, which are important for binding to actin. Unfortunately, disorder in binding and the variable twist of F-actin obscure the three-dimensional structure of utrophin–actin complexes seen under the electron microscope, making detailed studies problematic. Galkin et al. tackled this problem with their recently developed...