Amino acid sequences internal repeats

Determination of the amino-acid sequence of human serum transferrin (MacGillivray et ah, 1983) and of human lactoferrin (Metz-Boutique etal., 1984) revealed an internal two-fold sequence repeat. The amino-terminal half has approximately 40 % sequence identity with the carboxyl-terminal half. Similar results have subsequently been found for a number of other transferrins (Baldwin,... 

When the complete amino acid sequence of ceruloplasmin was determined, an internal threefold repeat suggested gene triplication (Ta-kahashi et al., 1983). Moreover, sequence similarity to the small blue copper domains suggested that there were at least two domains with blue copper-binding sites. Analysis of fragments of laccase sequence indicated that there might be a relationship of this to small blue proteins and ceruloplasmin as well (Ryden, 1988). 

The large size of transferrins (670-700 residues), with the consequent difficulties of chemical sequencing, meant that it was not until 1982 that the first amino acid sequences, those of human serum transferrin 10) and chicken ovotransferrin 34,35), were established. These were closely followed by that of human lactoferrin 11). The twofold internal repeat in each sequence (see below) was immediately apparent, and comparison of all three sequences then identified conserved tyrosines and histidines that were potential ligands for iron (11). 

Of fundamental significance to understanding transferrin structure and function is the two-fold internal amino acid sequence repeat. In each protein, the N-terminal half of the polypeptide is homologous with the C-terminal half, with the level of identity between the two halves ranging from 26-28% in the insect proteins to —40% in higher transferrins and as high as 46% in melanotransferrin. This repeat is expressed... 

Amino acid sequences can be searchedfor the presence of internal repeats. Such internal repeats can reveal information about the history of an individual protein itself Many proteins apparently have arisen by duplication of a primordial gene followed by its diversification. For example, calmodulin, a ubiquitous calcium sensor in eukaryotes, contains four similar calcium-binding modules that arose by gene duplication (Figure 4.28). 

Figure 7.15. A Self-Diagonal Plot For the TATA-Box-Binding Protein From the YXant Arabidopsis. Self-diagonal plots are used to search for amino acid sequence repeats within a protein. The central diagonal is the sequence aligned with itself Red dots indicating a correspondence of amino acids appear where two or more amino acids in a row match. Lines of dots, highlighted in pink, parallel to the central diagonal suggest an internal repeat.

Amino acid sequences can be searched for the presence of internal repeats. Such internal repeats can reveal the history of an individual protein itself. 

C -Keratin, which is the primary component of wool and hair, consists of two right-handed o helices intertwined to form a type of left-handed superhelix called an a coiled coil, ot-Keratin is a member of a superfamily of proteins referred to as coiled-coil proteins (Figure 2,43). In these proteins, two or more a helices can entwine to form a verv stable structure, which can have a length of 1000 A (100 nm, or 0.1 jiim) or more. There are approximately 60 members of this family in humans, including intermediate filaments, proteins that contribute to the cell cytoskeleton (internal scaffolding in a cell), and the muscle proteins myosin and tropomyosin (Section 34.2). Members of this family are characterized by a central region of 300 amino acids that contains imperfect repeats ol a sequence of seven amino acids called a heptad repeal. 

The sequence of riboflavin synthase of B. subtilis, the first that became available, was determined at the protein level by Edman sequencing and, independently, by DNA sequencing. "" In line with the hypothesis that the enzyme could provide a pseudo-C2-symmetric environment, it was gratifying to observe that the 215 amino acid peptide shows strong internal sequence homology specifically, 26 amino acids in the internal sequence repeat of the B. subtilis enzyme are identical and 23 are similar (Figure 12). "" ... 

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