Repeated folding pattern in copper–zinc superoxide dismutase

Abstract

Some globular proteins contain repeated structural patterns within the same polypeptide chain. Several enzymes^1–9 have a pseudo-symmetric two-lobed architecture: a pair of connected but well separated domains with very similar structures are grouped round an approximate 2-fold symmetry axis close to the active centre. On a smaller scale the same motif may appear inside a single protein domain: the polypeptide chain folds into two successive topologically similar subdomains which interlock symmetrically and form a compact globule^10–16. In such a domain the two halves come into close contact round the dyad axis; as if the structural integrity of the domain depended on the interactions between its halves, while one separated subdomain could not exist as an independent folding unit. Many of these paired structures seem to have evolved from dimeric precursors by tandem gene duplication^17–19. They contain repeated amino acid sequences or precisely repeated structural elements^3,6,13,20 in which equivalent sets of α-carbon atoms can be superimposed with root mean square deviations of the order of 1–2 Å. Here it is shown that copper–zinc superoxide dismutase^21–23 contains two paired subdomains, and the significance of the repeated folding pattern is discussed.