GLYCINE LOOPS IN PROTEINS - THEIR OCCURRENCE IN CERTAIN INTERMEDIATE FILAMENT CHAINS, LORICRINS AND SINGLE-STRANDED RNA-BINDING PROTEINS

Quasi-repetitive, glycine-rich peptide sequences are widespread in at least three distinct families of proteins: the keratins and other intermediate filament proteins, including nuclear lamins; loricrins, which are major envelope components of terminally differentiated epithelial cells; and single-stranded RNA binding proteins. We propose that such sequences comprise a new structural motif termed the 'glycine loop'. The defining characteristics of glycine loop sequences are: (1) they have the form x(y)n, where x is usually an aromatic or occasionally a long-chain aliphatic residue; y is usually glycine but may include polar residues such as serine, asparagine, arginine, cysteine, and rarely other residues; and the value of n is highly variable, ranging from 1 to 35 in examples identified to date. (2) Glycine-loop-containing domains are though to form when at least two and to date, as many as 18, such quasi-repeats are configured in tandem, so that the entire domain in a protein may be 50-150 residues long. (3) The average value of n, the pattern of residues found in the x position and the non-glycine substitutions in the y position appear to be characteristic of a given glycine loop containing domain, whereas the actual number of repeats is less constrained. (4) Glycine loop sequences display a high degree of evolutionary sequence variability and even allelic variations among different individuals of the same vertebrate species. (5) Glycine loop sequences are expected to be highly flexible, but possess little other regular secondary structure. It is hypothesized that glycine loop motifs in a given domain may organize into higher-order structures anchored on packing of the x residues, and that multiple interactions between configurations of the neighbouring glycine loops on the same or adjacent different protein molecules may form the basis for adaptable intra-cytoskeletal and envelope-cytoskeletal interactions in the epidermis. In view of the few residues that are involved in glycine loops, their high abundance when they do occur, and the likelihood that individual glycine loops do not have uniquely defined conformation, n.m.r. spectroscopy appears to offer the best prospects to investigate the implications of these proposals.