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Design of a discretely folded mini-protein motif with predominantly β-structure

Nature Structural Biology volume 8, pages 535–539 (2001)Cite this article

Abstract

Here we report the creation of a predominantly β-structured mini-protein motif. The design target is based on the naturally occurring toxin hand (TH) motifs that are composed of four disulfide bonds and three loops that form a 'hand'. Analysis and subsequent modification of several generations of mini-proteins produced the final 29-residue mini-protein. The structured motif of this new mini-protein provides insight into the compensatory changes that result in the formation of a tightly packed hydrophobic core in a small, globular β-structure motif. Additionally, this mini-motif represents a new, distinct surface topology for protein design and a valuable, yet compact, model system for the study of β-sheet structure in water.

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Figure 1: Ribbon diagrams of the toxin hand motifs.
Figure 2: Peptides synthesized in the process of developing a discretely folded motif.
Figure 3: Key NMR data for TH-1ox, TH-10Aox and TH-10Box.
Figure 4: NMR-derived structures.

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Acknowledgements

This research was supported by the NSF. The award of NSF predoctoral fellowship to J.J.O., the Multiuser Facility for the Study of Complex Macromolecular Systems, the Francis Bitter Magnet Labs and the Department of Chemistry Instrumentation Facility are also gratefully acknowledged.

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  1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Jennifer J. Ottesen & Barbara Imperiali

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  1. Jennifer J. Ottesen
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  2. Barbara Imperiali
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Correspondence to Barbara Imperiali.

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Ottesen, J., Imperiali, B. Design of a discretely folded mini-protein motif with predominantly β-structure. Nat Struct Mol Biol 8, 535–539 (2001). https://doi.org/10.1038/88604

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