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Membrane enzymes

Transformers at the interface

Nature Chemical Biology volume 11, pages 102–103 (2015)Cite this article

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Recent studies on two enzyme classes operating at the membrane interface showcase an unanticipated degree of structural plasticity involving domain swapping and marked secondary structure reshuffling. This structural variability in topology is key to functional diversification and catalytic prowess.

Membrane enzymes constitute a large class of proteins with vital roles in cellular signaling and metabolism and typically act on membrane components as substrates such as lipids or oligosaccharides of the bacterial cell wall1. The molecular basis of diverse reaction specificities of closely related membrane enzymes transforming identical substrates into different products has been largely elusive. Now, a study by Palczewski and colleagues2 discloses a fundamental principle of how nature propels functional diversification of existing scaffolds. These authors discovered that a rather small, genetically encoded loop insertion of just 30 amino acids makes a big structural difference between two connate human membrane enzymes by providing a platform for domain swapping, leading to active site remodeling and altered reaction specificity2. Another exciting example of large-scale structural rearrangements for an enzyme at the membrane interface was reported by Alzari, Guerin and colleagues3, who studied a mycobacterial glycosyltransferase and found it to undergo a series of marked structural transitions in response to substrate and lipid binding. This involves transformations of α-helices into β-strands and vice versa in a remarkable domain reshuffling with fluctuating topologies. The studies by Golczak et al.2 and Giganti et al.3 thus impressively illustrate that membrane enzymes are not merely doing 'a little molecular gymnastics'; rather, they are powerful transformers with unanticipated structural flexibility playing 'TopoLego' with secondary structure elements.

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Figure 1: Structural flexibility of interfacial membrane enzymes.

References

  1. Forneris, F. & Mattevi, A. Science 321, 213–216 (2008).

    CAS  Article  Google Scholar 

  2. Golczak, M., Sears, A.E., Kiser, P.D. & Palczewski, K. Nat. Chem. Biol. 10.1038/nchembio.1687 (10 November 2014).

  3. Giganti, D. et al. Nat. Chem. Biol. 10.1038/nchembio.1694 (17 November 2014).

  4. Golczak, M. et al. J. Biol. Chem. 287, 23790–23807 (2012).

    CAS  Article  Google Scholar 

  5. Neumann, P. & Tittmann, K. Curr. Opin. Struct. Biol. 29, 122–133 (2014).

    CAS  Article  Google Scholar 

  6. Liu, Y. & Eisenberg, D. Protein Sci. 11, 1285–1299 (2002).

    CAS  Article  Google Scholar 

  7. Von Heijne, G. Nat. Rev. Mol. Cell Biol. 7, 909–918 (2006).

    CAS  Article  Google Scholar 

  8. Guerin, M.E. et al. J. Biol. Chem. 282, 20705–20714 (2007).

    CAS  Article  Google Scholar 

  9. Neumann, P., Weidner, A., Pech, A., Stubbs, M.T. & Tittmann, K. Proc. Natl. Acad. Sci. USA 105, 17390–17395 (2008).

    CAS  Article  Google Scholar 

  10. Henzler-Wildman, K.A. et al. Nature 450, 913–916 (2007).

    CAS  Article  Google Scholar 

Download references

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  1. Florian Brodhun & Kai Tittmann are in the Department of Molecular Enzymology, Göttingen Center for Molecular Biosciences, Georg-August University Göttingen, Göttingen, Germany.

    Florian Brodhun & Kai Tittmann

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  1. Florian Brodhun
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  2. Kai Tittmann
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Correspondence to Kai Tittmann.

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The authors declare no competing financial interests.

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Brodhun, F., Tittmann, K. Transformers at the interface. Nat Chem Biol 11, 102–103 (2015). https://doi.org/10.1038/nchembio.1738

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