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The dystrophin protein

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.

Domain sub domain amino acids exons


actin binding domain 14-240 2-8

central rod domain 253-3040 8-61


hinge 1 253-327 (8)-9
repeat 1 337-447 10-11
repeat 2 448-556 12-14
repeat 3 557-667 14-16
hinge 2 668-717 17
repeat 4 718-828 (17)-20
repeat 5 829-934 20-21
repeat 6 935-1045 22-23
repeat 7 1046-1154 (23)-(26)
repeat 8 1155-1263 26-27
repeat 9 1264-1367 28-(30)
repeat 10 1368-1463 30-32
repeat 11 1464-1568 32-(34)
repeat 12 1569-1676 34-35
repeat 13 1677-1778 36-37
repeat 14 1779-1874 38-(40)
repeat 15 1875-1973 40-41
interruption 1974-1991 42
repeat 16 1992-2101 42-43
repeat 17 2102-2208 44-45
repeat 18 2209-2318 46-48
repeat 19 2319-2423 48-50
hinge 3 2424-2470 50-51
repeat 20 2471-2577 51-53
repeat 21 2578-2686 53-(55)
repeat 22 2687-2802 55-(57)
repeat 23 2803-2931 57-59
repeat 24 2932-3040 59-(61)
hinge 4 3041-3112 61-64
Cysteine-rich domain 3080-3360 63-69
dystroglycan binding site 3080-3408 63-70
WW domain 3056-3092 62-63
EF-hand 1 3130-3157 65
EF-hand 2 3178-3206 65-66
ZZ domain 3307-3354 68-69
Carboxy-terminal domain 3361-3685 70-79
alpha1-syntrophin binding site 3444-3494 73-74
ß1-syntrophin binding site 3495-3535 74-75
(Leu)6-heptad repeat 3558-3593 75

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

Evolution

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