The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein

@article{Koenig1988TheCS,
  title={The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein},
  author={M. Koenig and A. Monaco and L. Kunkel},
  journal={Cell},
  year={1988},
  volume={53},
  pages={219-228}
}
The complete sequence of the human Duchenne muscular dystrophy (DMD) cDNA has been determined. The 3685 encoded amino acids of the protein product, dystrophin, can be separated into four domains. The 240 amino acid N-terminal domain has been shown to be conserved with the actin-binding domain of alpha-actinin. A large second domain is predicted to be rod-shaped and formed by the succession of 25 triple-helical segments similar to the repeat domains of spectrin. The repeat segment is followed by… Expand
An autosomal transcript in skeletal muscle with homology to dystrophin
THE Duchenne muscular dystrophy (DMD) gene has been localized to chromosome Xp211–6 and codes for a 14-kilobase (kb) transcript7 and a protein called dystrophin8, of relative molecular mass 427,000.Expand
Exogenous Dp71 is a dominant negative competitor of dystrophin in skeletal muscle
TLDR
Dp71, which consist of the C-terminal and the cysteine-rich domains of dystrophin, is the major product of the gene in all non-muscle tissues tested so far, but it is absent in differentiated skeletal muscle. Expand
The structure of the N-terminal actin-binding domain of human dystrophin and how mutations in this domain may cause Duchenne or Becker muscular dystrophy.
TLDR
Examining the position of three pathogenic missense mutations within the structure suggests that they exert their effects through misfolding of the ABD, rather than through disruption of the binding to F-actin. Expand
Spectrin-like repeats from dystrophin and alpha-actinin-2 are not functionally interchangeable.
TLDR
A chimeric transgene containing the four-repeat rod domain of alpha-actinin-2 was expressed in mdx mice, and data demonstrated that different spectrin-like repeats are not equivalent, and reinforced the suggestion that the dystrophin rod domain is not merely a spacer but likely contributes an important mechanical role to overall dyStrophin function. Expand
Spectrin-like repeats from dystrophin and α-actinin-2 are not functionally interchangeable
TLDR
A chimeric transgene containing the four-repeat rod domain of alpha-actinin-2 was expressed in mdx mice, and data demonstrated that different spectrin-like repeats are not equivalent, and reinforced the suggestion that the dystrophin rod domain is not merely a spacer but likely contributes an important mechanical role to overall dyStrophin function. Expand
From the spectrin gene to the assembly of the membrane skeleton.
TLDR
Comparison of the deduced amino acid sequence shows that alpha-spectrin is well conserved in different species and that the human erythrocyte alpha-Spectrin is divergent. Expand
Structural predictions for the central domain of dystrophin
TLDR
It is proposed that whilst the repeating structural motif in dystrophin is probably a bead of triple coiled coil, this bead is twice as massive as, and out of phase with, those proposed for spectrin, which raises the possibility that the rod domain of dyStrophin may confer elasticity on the molecule. Expand
Minimum folding unit of dystrophin rod domain.
TLDR
It appears that the minimum unit capable of forming the native fold extends some residues into the adjoining sequence repeat, and the fragment of 119 residues forms a significantly more stable structure than that of 117, which was found that the critical length for folding was 117 residues. Expand
Structural cooperativity in spectrin type repeats motifs of dystrophin.
TLDR
This work examines three spectrin-type-repeat motifs in dystrophin, expressing them recombinantly both singly and in tandem, and studying their thermodynamic properties by solvent and thermal denaturation, finding that the degree to which they are independently stable and expressible varies considerably. Expand
Primary structure and domain organization of human alpha and beta adducin
TLDR
The complete sequence of both subunits of human adducin, alpha (737 amino acids), and beta (726 amino acids) has been deduced by analysis of the cDNAs, suggesting evolution by gene duplication. Expand
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References

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TLDR
Northern blots reveal only one size class of mRNA in fibroblasts and smooth muscle, but no hybridizing species could be detected in skeletal muscle poly(A+) RNA, consistent with the view that smooth and skeletal muscle alpha-actinins are encoded by separate genes. Expand
Erythrocyte spectrin is comprised of many homologous triple helical segments
TLDR
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TLDR
It is shown that dystrophin is associated with the triadic junctions in skeletal muscle, and is therefore probably involved with Ca2+ homoeostasis, and shown that the ∼450K ryanodine receptor/sarcoplasmic reticulum Ca1+ channel8, which has the large size and subcellular distribution characteristics of dyStrophin, is an immunologically distinct protein species. Expand
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TLDR
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TLDR
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TLDR
The nucleotide sequence of two highly conserved DNA fragments from the DXS164 locus and their homologous sequences from the mouse X chromosome are presented and are candidates for portions of the gene responsible for both DMD and BMD. Expand
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TLDR
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TLDR
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TLDR
The 14 kb human Duchenne muscular dystrophy cDNA corresponding to a complete representation of the fetal skeletal muscle transcript has been cloned and the majority of deletions are concentrated in a single genomic segment corresponding to only 2 kb of the transcript. Expand
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TLDR
A molecular mechanism to explain the clinical difference in severity between DMD and BMD patients who bear partial deletions of the same gene locus is presented and is applicable to potential 5' and 3' intron splice mutations and their effect on protein production and clinical phenotype. Expand
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