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The N‐terminal actin binding domain (ABD1) of dystrophin is in a closed conformation in solution and undergoes a conformational transition upon binding to F‐actin
Author(s) -
Mallela Krishna,
Singh Surinder
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.773.5
Subject(s) - dystrophin , calponin , dimer , actin , chemistry , biophysics , conformational change , crystallography , monomer , protein structure , stereochemistry , biochemistry , biology , polymer , organic chemistry , gene
Deficiency of the vital muscle protein dystrophin triggers Duchenne/Becker muscular dystrophy. Dystrophin stabilizes muscle cells against forces associated with muscle contraction and stretch. It interacts with F‐actin using its N‐terminal actin‐binding domain (N‐ABD or ABD1), which is comprised of tandem calponin‐homology (CH) domains. A previously determined X‐ray crystal structure indicated that the N‐ABD is a domain‐swapped dimer, with each monomer adopting an ‘open’ conformation in which the two CH domains do not interact. This structure is controversial as it contradicts known structures of similar domains in other muscle proteins. Here we investigated the conformation of dystrophin N‐ABD in solution using a simple and elegant technique of pyrene excimer fluorescence. Our results clearly indicate that dystrophin N‐ABD is a monomer in solution and is in a ‘closed’ conformation in which the two CH domains appear to interact. Upon binding to F‐actin, this domain transitions into a more compact closed conformation. This study demonstrates for the first time the conformational transition of a dystrophin domain during function, and suggests that such structural dynamics play important role in controlling dystrophin function.