An inverse correlation between loop length and stability in a four-helix-bundle protein.

A D Nagi; L Regan

doi:10.1016/s1359-0278(97)00007-2

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An inverse correlation between loop length and stability in a four-helix-bundle protein.

A D Nagi·L Regan

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Abstract

BACKGROUND: The loops in proteins are less well characterized than the secondary structural elements that they connect. We have used the four-helix-bundle protein Rop as a model system in which to explore the role of loop length in protein folding and stability. RESULTS: A natural two-residue loop was replaced with a series of glycine linkers up to 10 residues in length. All 10 mutants are highly helical dimers that retain wild-type RNA-binding activity. As loop length is increased, the stability of Rop toward thermal and chemical denaturation is progressively decreased. CONCLUSIONS: All the mutants assume a wild-type-like structure, which suggests that the natural loop does not actively dictate the final protein fold. The strong inverse correlation observed between loop length and stability is well described by a simple polymer model in which the entropy of loop closure is the dominant energetic term. Our results emphasize the importance of optimization of loop length to successful protein design.

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Cloning, Molecular Diterpenes Models, Chemical Models, Structural Polymerase Chain Reaction Protein Conformation Protein Engineering Protein Folding Statistics as Topic Thermodynamics Ultracentrifugation Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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A D Nagi, L Regan. 1997. An inverse correlation between loop length and stability in a four-helix-bundle protein.. https://doi.org/10.1016/s1359-0278(97)00007-2

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