Abstract
Many proteins contain a repetitive sequence motif, which implies that they contain a repetitive structural motif. Spectrin and the related proteins dystrophin and alpha-actinin consist largely of repeated motifs of 100-120 residues. But the repeating motif is degenerate and it has been difficult to define the boundaries of the repeating sequence unit or its corresponding structural unit. We have determined at which residues the structural units that correspond to spectrin's repeating 106-amino acid motifs begin and end. Drosophila alpha-spectrin cDNAs were expressed in bacteria to show that single segments (106 amino acids) and pairs of segments encoded by selected regions of spectrin cDNA can fold into stable conformations whose biophysical and biochemical properties are similar to those of native spectrin. Because such folding was critically dependent on the phasing of the expressed sequence with respect to the apparent boundaries of the repeating motifs, our data provide experimental evidence that relates the boundaries of the folded, conformational unit to the chemical sequence of repeating motifs.
