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Structure of interleukin 16 resembles a PDZ domain with an occluded peptide binding site

Nature Structural Biology volume 5, pages 682–686 (1998)Cite this article

Abstract

The structure of a folded core of IL-16 is similar to that of intracellular protein modules called PDZ domains. IL-16 is thus the first extracellular protein found to have a PDZ-like fold. However, it does not exhibit normal peptide binding properties of PDZ domains. This is due to alterations of the structure at the 'PDZ-like binding site' of IL-16 (the GLGF cleft): the GLGF cleft of IL-16 is much smaller than those of PDZ-domains and is additionally blocked with a tryptophan side chain at its center. Our experiments indicate also that IL-16 nonspecifically aggregates in solution; but formation of a homo-tetrameric protein is not required, in contrast to previous suggestions, for its chemo-attractant activity.

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Figure 1: a, Steady-state heteronuclear 15N{1H}-NOE for the backbone amides of IL-16.
Figure 2: a, Backbone overlay of NMR structures of human IL-16 (residues 28-118).
Figure 3: Sequence alignment of human IL-16, synaptic protein third domain (PSD-95)34, Discs-Large (DLG482–566)24, ZO1408–491, ZO293–176, p5567–153, NOS12–100 and syntrophin (bSYN265–152)22.
Figure 4: a, Comparison of the overall topologies of IL-16 and Dlg_A.

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Acknowledgements

We thank R. Engh for stimulating discussions, F. Hesse for protein purification, H. Burtscher for cloning and expression, H. Popp for fermentation, M. Wozny for mass analysis and R. Rudolf for analytical ultracentrifugation. M. Z. is a recipient of the graduate scholarship from Verband der Chemischen Industrie.

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Authors and Affiliations

  1. Max Planck Institute for Biochemistry, Am Klopferspitz 18a, Martinsried, D-82152, F.R.G., Germany

    Peter Mühlhahn, Markus Zweckstetter, Julia Georgescu, Cornelia Ciosto & Christian Renner

  2. Boehringer Mannheim Biotechnology Research Center, Nonnenwald 2, Penzberg, D-82372, F.R.G. , Germany

    Martin Lanzendörfer, Kurt Lang & Dorothee Ambrosius

  3. Paul Ehrlich Institute, Paul-Ehrlich-Str. 51-59, Langen, D-63225, F.R.G., Germany

    Michael Baier, Reinhard Kurth & Tad A. Holak

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  1. Peter Mühlhahn
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Correspondence to Tad A. Holak.

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Mühlhahn, P., Zweckstetter, M., Georgescu, J. et al. Structure of interleukin 16 resembles a PDZ domain with an occluded peptide binding site. Nat Struct Mol Biol 5, 682–686 (1998). https://doi.org/10.1038/1376

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