Effects of deleting a tripeptide sequence observed in muscular dystrophy patients on the conformation of synthetic peptides corresponding to the scaffolding domain of caveolin-3.
The caveolin-scaffolding domain (CSD) is a region in caveolin-1 and 3 that mediates interactions with signaling proteins. In some patients with limb-girdle muscular dystrophy, a three amino acid micro deletion in the CSD has been observed. The conformations and aggregation behavior of synthetic peptides, corresponding to the CSD of caveolin-3: DGVWKVSYTTFTVSKYWFY and the sequence where TFT (underlined in the native sequence) has been deleted, have been investigated. Circular dichroism spectra and molecular dynamics simulations indicate distinctive differences in the conformations of the native and mutant sequences. The extent of self-association in aqueous medium is also less pronounced in the case of the peptide with the micro deletion. It is likely that the structural changes arising as a result of TFT deletion distrupt oligomerization and consequently mistargeting and degradation.
Jagannadham
M V
MV
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
Sharadadevi
A
A
Nagaraj
R
R
D000595:Amino Acid Sequence; D051244:Caveolin 3; D022461:Caveolins / Q000138:chemical synthesis / Q000737:chemistry*; D002942:Circular Dichroism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics; D009842:Oligopeptides / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion
C468291:CSD 16; C468290:CSD 19; D051244:Caveolin 3; D022461:Caveolins; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides