Stability of the dystrophin rod domain fold: evidence for nested repeating units.
An examination of fragments of the human dystrophin rod domain, corresponding to a single structural repeating unit, showed that a critical chain length, defined with a precision of one residue at the C-terminal end, is required for formation of the native tertiary fold. We report here that extending the chain by six residues beyond this minimum results in a large increase in conformational stability. This is not related to a change in association state of the polypeptide. The results support the conjecture that successive repeating units in the rod domain of the spectrinlike proteins form a nested structure, in which the N-terminal part of the three-helix bundle of one repeat packs into the overlapping structure of the preceding repeat. This would be expected to affect functional characteristics related to flexibility of the dystrophin rod domain.
Calvert
R
R
Medical Research Council Muscle and Cell Motility Unit, King's College, London, UK.
Kahana
E
E
Gratzer
W B
WB
D000595:Amino Acid Sequence; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002942:Circular Dichroism; D004330:Drosophila; D016189:Dystrophin / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D013049:Spectrin / Q000737:chemistry / Q000235:genetics; D013816:Thermodynamics
D016189:Dystrophin; D010446:Peptide Fragments; D013049:Spectrin