The Structure of Transthyretin Prealbumin

Transthyretin (TTR) is one of the most completely characterized human proteins. The TTR molecule is a stable and symmetrical tetramer composed of four identical subunits with a molecular weight of 54,980 (Kanda et al., 1974). Tire complete amino acid sequence of the human TTR subunit is shown in Fig. 1. The fiill three-dimensional structure of the human TTR molecule has been elucidated by X-ray crystallographic studies at 6-A (Blake et al., 1971), at 2.5-A (Blake et al., 1974), and at 1.8-A (Blake et al., 1978) resolution. These studies have shown that the subunits have extensive p-sheet structure, are arranged tetra-hedrally, and are linked into stable dimers, each comprising two of the four 

In the human, TTR is one of three plasma proteins involved in the transport of the thyroid hormones in blood (Ingbar, 1963 Oppenheimer, 1968). The principal transport protein for thyroid hormones in human plasma is thyroxine-binding globulin, and TTR plays only a lesser role in the normal transport and metabolism of thyroid hormones in man (Woeber and Ingbar, 1968). In the rat, however, TTR appears to be the major thyroid hormone transport protein (Davis et al., 1970 Sutherland and Brandon, 1976). 

TTR isolated from serutii of other mammalian and avian species greatly resembles human TTR (see below). Rhesus monkey TTR displays genetic polymorphism, which is not present in the human. The partial amino-terminal sequences of the TTR subunit from the rhesus monkey (van Jaarsveld et al., 1973b) and from the rat (Navab et al., 1977a) arc extrcmely similar to that of human TTR. 

High-resolution X-ray crystallographic studies have shown that the TTR molecule contains two surface sites with structural complementarity to double-helical DNA (Blake and Oatley, 1977). Although the binding of TTR to DNA has not been reported, it has been suggested that the TTR molecule may serve as a model for the kind of structure that may be involved in hormone receptors with nuclear effects on DNA transcription (Blake and Oatley, 1977 Blake, 1981). 

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