Dystrophin is a rod-shaped protein, measuring about 150 nm, consisting of 3684
amino acids with a calculated molecular weight of 427 kDa. Dystrophin is predominantly hydrophilic throughout its entire length and 31% of the amino-acids are charged (i.e. Arg, Asp, Glu, His and Lys). A "Chou and Fasman" prediction of secondary structure reveals a very high potential for an alpha-helical formation over the majority of the sequence. Dystrophin can be separated into four domains:
actin binding domain (amino acids 14-240):
this region contains a putative actin-binding region and was discovered by its homology with chicken alpha-actinin (Hammonds). alpha-actinin is a normal component of the actin filaments in smooth and skeletal muscle and is probably involved in cross-linking F-actin and thereby connecting the filamentous elements of the cytoskeleton to the cell membrane. central rod domain (amino acids 253-3040): a large central domain formed by 24 spectrin-like triple-helical elements of about 109 amino acids with homology to alpha-actinin and spectrin. The repeats are interrupted by four proline-rich non-repeat segments, the so called hinge regions. Repeats 15 and 16 are separated by an 18 amino acid stretch which seems a major site for proteolytic cleavage of dystrophin (Koenig). The identity between most repeats ranges from 10-25%. One repeat contains three alpha-helices: 1, 2 and 3. Apha-helices 1 and 3 are each formed by 7 helix turns, probably interacting as a coiled-coil through a hydrophobic interface. Alpha-helix 2 has a more complex structure and is formed by segments of four and three helix turns, separated by a Glycine or Proline residue. Each repeat is encoded by two exons, always interrupted by an intron exactly between amino acids 47 and 48 in the first part of alpha-helix 2. The other intron is found at different positions in the repeat, usually scattered over helix- 3. Cysteine-rich domain (amino acids 3080-3360): a cysteine-rich segment (i.e. 15 Cysteines in 280 amino acids) showing homology to the C-terminal domain of the slime mold (Dictyostelium discoideum) alpha-actinin. The homologous region, amino acids 3115-3269 with 24% identity over 142 amino acids, includes two potential EF-hand Ca2+- binding sites although the dystrophin sequence does not match the consensus sequence for these EF-hands very well. Carboxy-terminal domain (amino acids 3361-3685): this 325 amino acid C-terminal domain does not show any homology to known proteins, except with the dystrophin related proteins.
Dp71 is phosphorylated in vitro by p34cdc2 protein kinase Milner 93, JBC 21:21901- 21905 (consensus site in exon 78 -TPGK-). Exon 1 encodes the 5'-untranslated region and 11 amino acids.
the protein
the dystrophin glycoprotein complex (DGC): dystrophin associated proteins
dystrophin isoforms: how they arise and their nomenclature dystrophin protein sequences Dp427m, Dp427l, Dp427c, Dp427p, Dp260, Dp140, Dp116, Dp71 and Dp40 dystrophin antibodies and their epitopes Dystrophin related sequences o dystrophin associated proteins o dystrophin related proteins / homologous proteins