A novel quaternary structure of the dimeric alpha-crystallin domain with chaperone-like activity.
alphaB-crystallin, a member of the small heat-shock protein family and a major eye lens protein, is a high molecular mass assembly and can act as a molecular chaperone. We report a synchrotron radiation x-ray solution scattering study of a truncation mutant from the human alphaB-crystallin (alphaB57-157), a dimeric protein that comprises the alpha-crystallin domain of the alphaB-crystallin and retains a significant chaperone-like activity. According to the sequence analysis (more than 23% identity), the monomeric fold of the alpha-crystallin domain should be close to that of the small heat-shock protein from Methanococcus jannaschii (MjHSP16.5). The theoretical scattering pattern computed from the crystallographic model of the dimeric MjHSP16.5 deviates significantly from the experimental scattering by the alpha-crystallin domain, pointing to different quaternary structures of the two proteins. A rigid body modeling against the solution scattering data yields a model of the alpha-crystallin domain revealing a new dimerization interface. The latter consists of a strand-turn-strand motif contributed by each of the monomers, which form a four-stranded, antiparallel, intersubunit composite beta-sheet. This model agrees with the recent spin labeling results and suggests that the alphaB-crystallin is composed by flexible building units with an extended surface area. This flexibility may be important for biological activity and for the formation of alphaB-crystallin complexes of variable sizes and compositions.
Feil
I K
IK
European Molecular Biology Laboratory (EMBL), EMBL Hamburg Outstation, Notkestrasse 85, D-22603 Hamburg, Germany. Feil@EMBL-Hamburg.DE
Malfois
M
M
Hendle
J
J
van Der Zandt
H
H
Svergun
D I
DI
D000595:Amino Acid Sequence; D018833:Chaperonins / Q000737:chemistry*; D002942:Circular Dichroism; D003001:Cloning, Molecular; D003459:Crystallins / Q000737:chemistry* / Q000235:genetics; D019281:Dimerization; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D013056:Spectrophotometry, Ultraviolet; D014961:X-Ray Diffraction
D003459:Crystallins; D018833:Chaperonins