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A domain-swapped RNase A dimer with implications for amyloid formation

Nature Structural Biology volume 8, pages 211–214 (2001)Cite this article

Abstract

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 α-helix with that of an identical molecule. Here we find that the major dimer forms by swapping its C-terminal β-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 β-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.

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Figure 1: Ribbon diagrams of the structures of RNase A.
Figure 2: Stereo view of the 2Fo - Fc electron density map of the inhibitor of RNase A, dCpdG, contoured at 1.4 σ to illustrate its detail.
Figure 3: Structure of the hinge loops of the RNase A major dimer with implications for amyloid fiber formation.

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Acknowledgements

We thank D. Cascio, O. Dym, D. Anderson and M. Sawaya for technical advice, I. Xenario, M. J. Bennett and G. Kleiger for useful discussion, and A. McPherson for generously providing coordinates of RNase A and d(pA)4 complex. This work was supported by NSF, NIH, DOE, and Italian MURST-Prin 1999.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry and Biological Chemistry, UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles, 90095-1570, California, USA

    Yanshun Liu & David Eisenberg

  2. Department of Neurological Science, Biological Chemistry Section, University of Verona, Verona, Italy

    Giovanni Gotte & Massimo Libonati

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  1. Yanshun Liu
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  2. Giovanni Gotte
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  3. Massimo Libonati
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  4. David Eisenberg
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Correspondence to David Eisenberg.

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Liu, Y., Gotte, G., Libonati, M. et al. A domain-swapped RNase A dimer with implications for amyloid formation. Nat Struct Mol Biol 8, 211–214 (2001). https://doi.org/10.1038/84941

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