Figure 1: Ribbon diagrams of the structures of RNase A. a, The monomer; b, the minor dimer; c, the major dimer; and d, a model of a trimer of a produced by combining panels b and c. The N and C termini are labeled. In the minor dimer, the N-terminal ahelices are swapped; in the major dimer, the C-terminal b strands are swapped. The closed interfaces are the interface between the blue segment and the green core structure, and the interface between the red segment and the green core structure in a, which are also found in the minor dimer (b) and the major dimer (c), respectively.
The open interface in the minor dimer lies between the green and the blue strands in the middle of the b sheet in b, and the open interface in the major dimer lies between the red and the green segments in the center of the molecule in c. These open interfaces do not exist in a. The core domain of the green subunit in each molecule has the same orientation. In the model of the trimer, domain swapping takes place at both the N and C termini. The figure was created using Raster3D.
From Liu, Y., Gotte, G., Libonati, M., and Eisenberg, D. 2001. Nature Structural Biology 8:211–214. © 2001 Nature Publishing Group.
Figure 2: Structure of the hinge loops of the RNase A major dimer, with implications for amyloid fiber formation. a, Structure of the open interface of the RNase A major dimer, showing the atomic structure for residues 110–117 of both molecules of the dimer. These segments correspond to the central portion of Figure 1. Carbon, nitrogen, and oxygen atoms are in yellow, blue, and red, respectively. Hydrogen bonds are shown as purple dots. Three hydrogen bonds are formed between Asn 113 residues in the two hinge loops. The atoms involved in these three hydrogen bonds are labeled. The figure is plotted with SETOR.
b, Speculative three-dimensional domain-swapping, polar-zipper model for formation of aggregates, with polyamide expansion loops. With the expansion of polyglutamine (PolyGln) in the hinge loop between two domains, a fluctuation that breaks the noncovalent bonds between the two domains exposes the polyglutamine loop as well as the two halves of the closed interface. The polyamide segment is able to form a b sheet, with three hydrogen bonds per residue pair, as observed for residue 113 in a. This stabilized sheet grows as additional polyamide b strands are added, defining the fiber axis perpendicular to the b strands, shown at the right. The sheet may be further stabilized by three-dimensional domain swapping formed by additional closed interfaces at the two sides of the sheet. A less-stable sheet could be formed by other (nonpolyamide) sequences and could account for the observation that proteins that undergo transition to the amyloid state exhibit enhanced b structure.
From Liu, Y., Gotte, G., Libonati, M., and Eisenberg, D. 2001. Nature Structural Biology 8:211–214. © 2001 Nature Publishing Group.
