Keep, NH; Winder, SJ; Moores, CA; Walke, S; Norwood, FLM; Kendrick-Jones, J; (1999) Crystal structure of the actin-binding region of utrophin reveals a head-to-tail dimer. STRUCT FOLD DES , 7 (12) 1539 - 1546.
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Background: Utrophin is a large multidomain protein that belongs to a superfamily of actin-binding proteins, which includes dystrophin, alpha-actinin, beta-spectrin, fimbrin, filamin and plectin. All the members of this family contain a common actin-binding region at their N termini and perform a wide variety of roles associated with the actin cytoskeleton. Utrophin is the autosomal homologue of dystrophin, the protein defective in the X-linked Duchenne and Becker muscular dystrophies, and upregulation of utrophin has been suggested as a potential therapy for muscular dystrophy patients.Results: The structure of the actin-binding region of utrophin, consisting of two calponin-homology (CH) domains, has been solved at 3.0 Angstrom resolution. It is composed of an antiparallel dimer with each of the monomers being present in an extended dumbell shape and the two CH domains being separated by a long central helix. This extended conformation is in sharp contrast to the compact monomer structure of the N-terminal actin-binding region of fimbrin.Conclusions: The crystal structure of the actin-binding region of utrophin suggests that these actin-binding domains may be more flexible than was previously thought and that this flexibility may allow domain reorganisation and play a role in the actin-binding mechanism. Thus utrophin could possibly bind to actin in an extended conformation so that the sites previously identified as being important for actin binding may be directly involved in this interaction.
|Title:||Crystal structure of the actin-binding region of utrophin reveals a head-to-tail dimer|
|Keywords:||actin binding, calponin-homology domain, dystrophin, utrophin, DYSTROPHIN-RELATED PROTEIN, CALPONIN HOMOLOGY DOMAINS, ALPHA-ACTININ, F-ACTIN, CROSS-LINKING, FIMBRIN-BINDING, DEFICIENT MICE, CH DOMAIN, SITE, MUSCLE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of)|
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