The N-terminal domain of beta B2-crystallin resembles the putative ancestral homodimer

beta gamma -crystallins from the eye lens are proteins consisting of two si milar domains joined by a short linker. All three-dimensional structures of native proteins solved so far reveal similar pseudo-2-fold pairing of the domains reflecting their presumed ancient origin from a single-domain homod imer. However, studies of engineered single domains of members of the beta gamma -crystallin superfamily have not revealed a prototype ancestral solut ion homodimer. Here we report the 2.35 Angstrom X-ray structure of the homo dimer of the N-terminal domain of rat beta B2-crystallin (beta B2-N). The t wo identical domains pair in a symmetrical manner very similar to that obse rved in native beta gamma -crystallins, where N and C-terminal domains (whi ch share similar to 35% sequence identity) are related by a pseudo-2-fold a xis. beta B2-N thus resembles the ancestral prototype of the beta gamma -cr ystallin superfamily as it self-associates in solution to form a dimer with an essentially identical domain interface as that between the N and C doma ins in beta gamma -crystallins, but without the benefit of a covalent linke r. The structure provides further evidence for the role of two-domain pairi ng in stabilising the protomer fold. These results support the view that th e beta gamma -crystallin superfamily has evolved by a series of gene duplic ation and fusion events from a single-domain ancestor capable of forming ho modimers. (C) 2000 Academic Press.