A betabellin is a beta-sandwich bell-shaped protein. It is a class of nongenetic b-sheet protein designed by Professor Jane S. Richardson (Duke University) and Professor Bruce W. Erickson (University of North Carolina at Chapel Hill) to test our understanding of the basic principles of protein folding.
The betabellin structure is a 32-residue peptide engineered to fold into a four-stranded antiparallel b-sheet protein (Richardson and Richardson, 1987; Lim et al., 1998). In most cases, the 32-residue betabellin peptide does not fold into a ? structure. However, when air oxidized to form a 64-residue disulfide-bridged homodimer, the betabellin peptide folds into a ? structure. Circular dichroism, mass spectrometry, electron microscopy, and electron paramagnetic resonance studies showed that betabellin 15D (B15D) binds Cu(II) ions and forms short broad fibrils (Lim et al., 1999). In addition, recent biophysical and ultrastructural studies indicated that B15D (a homodimer of HSLTAKIpkLTFSIAphTYTCAVpkYTAKVSH, where p = DPro, k = DLys, and h = DHis) forms unbranched, 35-Å wide protofilaments that associate into amyloid-like fibrils (Lim et al., 2000). These fibrils bind Congo red and display a green birefringence and exhibit a cross-? structure. These properties are characteristic of amyloidogenic proteins. As a result, with permission from the late Professor Erickson, we have initiated collaboration with Professor Dan Kirschner at Boston College to explore whether B15D can be used as a model for studying the molecular structure and self-assembly of cross-? fibrils.
Lim, A., Saderholm, M. J., Makhov, A. M., Kroll, M., Yan, Y., Perera, L., Griffith, J. D., and
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- Lim, A., Makhov, A. M., Bond, J., Inouye, H., Connors, L. H., Griffith, J. D., Erickson, B. W.,
- Kirschner, D. A., and Costello, C. E. (2000) Betabellins 15D and 16D, de novo designed beta-sandwich proteins that have amyloidogenic properties, J. Struct. Biol. 130, 363-370.
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