A domain-swapped RNase A dimer with implications for amyloid formation.
Bovine pancreatic ribonuclease (RNase A) forms two types of dimers (a major and a minor component) upon concentration in mild acid. These two dimers exhibit different biophysical and biochemical properties. Earlier we reported that the minor dimer forms by swapping its N-terminal alpha-helix with that of an identical molecule. Here we find that the major dimer forms by swapping its C-terminal beta-strand, thus revealing the first example of three-dimensional (3D) domain swapping taking place in different parts of the same protein. This feature permits RNase A to form tightly bonded higher oligomers. The hinge loop of the major dimer, connecting the swapped beta-strand to the protein core, resembles a short segment of the polar zipper proposed by Perutz and suggests a model for aggregate formation by 3D domain swapping with a polar zipper.
UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, Department of Chemistry and Biochemistry and Biological Chemistry, University of California, Los Angeles, California 90095-1570, USA.
Y
Y
Liu
G
G
Gotte
M
M
Libonati
D
D
Eisenberg
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D019281:Dimerization; D008958:Models, Molecular; D009711:Nucleotides / Q000378:metabolism; D058225:Plaque, Amyloid / Q000737:chemistry* / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000378:metabolism*; D012997:Solvents
D009711:Nucleotides; D012997:Solvents; D012259:Ribonuclease, Pancreatic