The N-terminal domain of betaB2-crystallin resembles the putative ancestral homodimer.
betagamma-crystallins from the eye lens are proteins consisting of two similar 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 homodimer. However, studies of engineered single domains of members of the betagamma-crystallin superfamily have not revealed a prototype ancestral solution homodimer. Here we report the 2.35 A X-ray structure of the homodimer of the N-terminal domain of rat betaB2-crystallin (betaB2-N). The two identical domains pair in a symmetrical manner very similar to that observed in native betagamma-crystallins, where N and C-terminal domains (which share approximately 35% sequence identity) are related by a pseudo-2-fold axis. betaB2-N thus resembles the ancestral prototype of the betagamma-crystallin superfamily as it self-associates in solution to form a dimer with an essentially identical domain interface as that between the N and C domains in betagamma-crystallins, but without the benefit of a covalent linker. The structure provides further evidence for the role of two-domain pairing in stabilising the protomer fold. These results support the view that the betagamma-crystallin superfamily has evolved by a series of gene duplication and fusion events from a single-domain ancestor capable of forming homodimers.
Clout
N J
NJ
Department of Crystallography, Birkbeck College, Malet Street, London, WC1E 7HX, UK.
Basak
A
A
Wieligmann
K
K
Bateman
O A
OA
Jaenicke
R
R
Slingsby
C
C
D000818:Animals; D001665:Binding Sites; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D019281:Dimerization; D019143:Evolution, Molecular; D006860:Hydrogen Bonding; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D038206:beta-Crystallin B Chain / Q000031:analogs & derivatives*
D003459:Crystallins; D038206:beta-Crystallin B Chain; C113634:beta-crystallin B2