Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Aug;20(4):482-8.
doi: 10.1016/j.sbi.2010.06.002. Epub 2010 Jun 28.

Proteins that switch folds

Philip N Bryan  1 , John Orban
Affiliations
Review

Proteins that switch folds

Philip N Bryan et al. Curr Opin Struct Biol. 2010 Aug.

Abstract

An increasing number of proteins demonstrate the ability to switch between very different fold topologies, expanding their functional utility through new binding interactions. Recent examples of fold switching from naturally occurring and designed systems have a number of common features: (i) The structural transitions require states with diminished stability; (ii) Switching involves flexible regions in one conformer or the other; (iii) A new binding surface is revealed in the alternate fold that can lead to both stabilization of the alternative state and expansion of biological function. Fold switching not only provides insight into how new folds evolve, but also indicates that an amino acid sequence has more information content than previously thought. A polypeptide chain can encode a stable fold while simultaneously hiding latent propensities for alternative states with novel functions.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A functional protein can switch into a completely different conformation with a different function via a mutational pathway in which neither function nor native structure is completely lost. The GA98 and GB98 proteins are only marginally stable, but restoration of close to wild type stability and function in either direction can be attained with only three mutations (e.g. to GA88 and GB88b).
Figure 2
Figure 2
Examples of naturally occurring ordered proteins that can exist in alternatively folded states. The structures of Ltn10, O-Mad2, and CLIC1(reduced) are color-coded as follows: β-strand (cyan), helix (red), and coil (yellow). The structures of the respective alternatively folded states Ltn40, C-Mad2, and CLIC1(oxidized), are shown with an identical per residue color code to illustrate the changes that take place in switching folds. (A) NMR structures of Ltn10 (PDB 1J8I, [54]) and Ltn40 (PDB 2JP1, [8]). A disulfide can be engineered between residues 21 and 59 in Ltn10 to prevent conformational switching. Only one of the subunits is colored in the Ltn40 homodimer. (B) NMR structures of O-Mad2 (PDB 1DUJ; [55]) and C-Mad2 (PDB 1S2H; [26]). Unchanged parts of the structure are in gray. (C) X-ray structures of the reduced (PDB 1K0M, [56]) and oxidized (PDB 1RK4, [31]) forms for the N-domains of CLIC1. The cysteine residues involved in disulfide formation are labeled in both states.
Figure 3
Figure 3
Conformational switching from 3-α GA to 4 β+α GB [9,14,15]. Regions of secondary structure in GB are color coded as follow β-strand (cyan), helix (red), and coil (yellow). The residues corresponding to these regions in the 3-α fold are colored in the same way to illustrate the extent of structural changes.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Anfinsen CB. Principles that govern the folding of protein chains. Science. 1973;181:223–230. - PubMed
    1. Wright PE, Dyson HJ. Linking folding and binding. Curr Opin Struct Biol. 2009;19:31–38. - PMC - PubMed
    1. Mottonen J, Strand A, Symersky J, Sweet RM, Danley DE, Geoghegan KF, Gerard RD, Goldsmith EJ. Structural basis of latency in plasminogen activator inhibitor-1. Nature. 1992;355:270–273. - PubMed
    1. Yamasaki M, Li W, Johnson DJ, Huntington JA. Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization. Nature. 2008;455:1255–1258. - PubMed
    1. Bullough PA, Hughson FM, Skehel JJ, Wiley DC. Structure of influenza haemagglutinin at the pH of membrane fusion. Nature. 1994;371:37–43. - PubMed

Publication types

LinkOut - more resources