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

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 beta (TGF beta). 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.

• Authors: T Meitinger, A Meindl, P Bork, B Rost, C Sander, M Haasemann, J Murken
• Journal: Nature genetics (Nat Genet) Vol. 5 Issue 4 Pg. 376-80 (Dec 1993) ISSN: 1061-4036 [Print] United States
• PMID: 8298646 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• von Willebrand Factor

Topics

• Amino Acid Sequence
• Blindness (genetics)
• Deafness (genetics)
• Humans
• Intellectual Disability (genetics)
• Models, Molecular
• Molecular Sequence Data
• Protein Structure, Tertiary
• Sex Chromosome Aberrations (genetics)
• X Chromosome
• von Willebrand Factor