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Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure

Nature Genetics volume 5, pages 376–380 (1993)Cite this article

Abstract

The X–lined gene for Norrie disease, which is characterized by blindness, deafness and mental retardation has been cloned recently. This gene has been thought to code for a putative extracellular factor; its predicted amino acid sequence is homologous to the C–terminal domain of diverse extracellular proteins. Sequence pattern searches and three–dimensional modelling now suggest that the Norrie disease protein (NDP) has a tertiary structure similar to that of transforming growth factor β (TGFβ). Our model identifies NDP as a member of an emerging family of growth factors containing a cystine knot motif, with direct implications for the physiological role of NDP. The model also sheds light on sequence related domains such as the C–terminal domain of mucins and of von Willebrand factor.

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Authors and Affiliations

  1. Abteilung für Pädiatrische Genetik, Kinderpoliklinik der Ludwig-Maximilians-Universität, Goethestrasse 29, 80336, München, Germany

    Thomas Meitinger, Alfons Meindl & Jan Murken

  2. European Molecular Biology Laboratory, 69012, Heidelberg, Germany

    Peer Bork, Burkhart Rost & Chris Sander

  3. Max Delbrück Center of Molecular Medicine, 13122, Berlin, Germany

    Peer Bork

  4. Institut Jacques Monod, 75251, Paris, France

    Martina Haasemann

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  1. Thomas Meitinger
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  6. Martina Haasemann
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  7. Jan Murken
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Meitinger, T., Meindl, A., Bork, P. et al. Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure. Nat Genet 5, 376–380 (1993). https://doi.org/10.1038/ng1293-376

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