Utrophin gets a new look

杨柳

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 image analysis algorithm, which can separate classes of polymorphic structures that are indistinguishable by traditional techniques. First reported last year, the new method is rapidly gaining acceptance. It is now being used to study several other actin-binding proteins, as well as protein–DNA interactions during recombination.
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' D6 V9 i8 D# PPrevious work identified only one type of utrophin binding to actin, but the new study shows that the utrophin actin-binding domain binds to F-actin in two distinct modes with different stoichiometries. The CH domains appear to bind in an extended conformation in both modes, as earlier X-ray crystallography studies had predicted. The two binding modes, and their fit within structural models, suggest that utrophin can establish different interactions with actin on multiple surfaces of actin subunits. Previous work has shown that other actin-binding proteins may exhibit similar diversity in their interactions, suggesting that multiple binding modes are a general theme allowing a small number of actin-binding proteins to create a diverse array of structures.(Utrophin (green) can bind to actin (ligh)