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Regulation of a muralytic enzyme by dynamic membrane topology

Nature Structural & Molecular Biology volume 16, pages 1192–1194 (2009)Cite this article

Abstract

R21, the lysozyme of coliphage 21, has an N-terminal signal-anchor-release (SAR) domain that directs its secretion in a membrane-tethered, inactive form and then its release and activation in the periplasm. Both genetic and crystallographic studies show that the SAR domain, once extracted from the bilayer, refolds into the body of the enzyme and effects muralytic activation by repositioning one residue of the canonical lysozyme catalytic triad.

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Figure 1: The R21 N-terminal domain and its physiological function.
Figure 2: Structural basis of R21 activation.

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Acknowledgements

We would like to acknowledge the contribution of E. McKee and E. Caronna in the structure determination of aR21. The work of Q.S., A.A. and J.C.S. was supported by funds to J.C.S. from the Robert A. Welch Foundation A-0015 and by US National Institutes of Health grant PO1AIO60342. The work of G.F.K., M.X. and R.Y. was supported by National Institutes of Health grant NIGMS27099 and by the Program for Membrane Structure and Function, a Program of Excellence grant from the Office of the Vice President for Research at Texas A&M University. Use of the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract no. DE-AC02-06CH11357.

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA

    Qingan Sun, Gabriel F Kuty, Ry Young & James C Sacchettini

  2. International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India

    Arulandu Arockiasamy

  3. Department of Microbiology, Immunology, & Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

    Min Xu

Authors
  1. Qingan Sun
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  2. Gabriel F Kuty
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  3. Arulandu Arockiasamy
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  4. Min Xu
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  5. Ry Young
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  6. James C Sacchettini
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Contributions

Q.S. determined the structure of iR21 and refined the structure of aR21 initially crystallized by A.A. Q.S. also performed the in vitro assays. G.F.K. did the molecular biology, genetics, physiology and bioinformatics. M.X. provided key constructs. R.Y. and J.C.S. provided supervision. The writing of the manuscript was a collaborative effort by Q.S., G.F.K., J.C.S. and R.Y.

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Correspondence to James C Sacchettini.

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Sun, Q., Kuty, G., Arockiasamy, A. et al. Regulation of a muralytic enzyme by dynamic membrane topology. Nat Struct Mol Biol 16, 1192–1194 (2009). https://doi.org/10.1038/nsmb.1681

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