Structural and functional implications of sequence repeats in fibrous proteins.

The amino acid sequences of increasingly large proteins have been determined in recent years, and it has become more and more apparent that within these sequences nature has employed only a finite number of structural?functional motifs. These may be strung along the sequence in tandem and, in some cases, several hundred times. In other instances, the positions of the motifs show little obvious order as regards to their relative linear arrangement within the sequence. The observed sequence repeats have been shown to vary in size over at least two orders of magnitude. It is shown here that the repeats can readily be classified on the basis of character, and five distinct groups have been identified. The first of these (Type A) represents those motifs that are fixed in length and conserved absolutely in sequence (>99%); the second (Type B) includes motifs that are also fixed in length, but where absolute sequence conservation occurs only in some positions of the repeat. The third category (Type C) contains fixed length motifs, but the character of only some of the positions in the motif is maintained. The fourth group (Type D) includes motifs that have nonintegral lengths. The fifth class (Type E) contains motifs, often displaying some variations in their lengths even within a single species, which maintain a discrete structural form related directly to their function. Examples are presented for each category of repeat, and these are drawn almost exclusively from the fibrous proteins and those proteins that are normally associated with them in vivo.