The N-terminal half of dystrophin is protected from proteolysis in situ.
Using a panel of "exon-specific" monoclonal antibodies, we have examined the products of degradation of dystrophin by endogenous proteases in post-mortem human muscle. Four main sites of dystrophin digestion were identified, all of them in the C-terminal half of the molecule. Two of them correspond to "hinges" in the central rod region and a third in the C-terminal domain follows the dystroglycan binding site. The results support the Koenig and Kunkel model for the tertiary structure of dystrophin (J. Biol. Chem. 265 (1990) 4560-4566), but suggest that much of the N-terminal half of dystrophin is protected from proteolysis, possibly by interaction with the sub-sarcolemmal cytoskeleton. Although the results seem inconsistent with an anti-parallel dimer model of dystrophin in which hinge 2 and hinge 3 are close together, possible ways of reconciling them with such a model are also considered.
Hori
S
S
Dept. of Molecular and Cellular Neurobiology, Tokyo Metropolitan Inst. for Neuroscience, Japan.
Ohtani
S
S
Nguyen
T M
TM
Morris
G E
GE
D000911:Antibodies, Monoclonal; D001665:Binding Sites; D015153:Blotting, Western; D016189:Dystrophin / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D005091:Exons; D006801:Humans; D008961:Models, Structural; D018482:Muscle, Skeletal / Q000378:metabolism*; D011180:Postmortem Changes; D017434:Protein Structure, Tertiary
D000911:Antibodies, Monoclonal; D016189:Dystrophin; D010450:Endopeptidases