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: DGVWKVSYTVSKYWFY 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. (C) 2002 Elsevier Science (USA). All rights reserved.