Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure.
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.
Meitinger
T
T
Abteilung für Pädiatrische Genetik, Ludwig-Maximilians-Universität, München, Germany.
Meindl
A
A
Bork
P
P
Rost
B
B
Sander
C
C
Haasemann
M
M
Murken
J
J
D000595:Amino Acid Sequence; D001766:Blindness / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012729:Sex Chromosome Aberrations / Q000235:genetics*; D014960:X Chromosome; D014841:von Willebrand Factor
D014841:von Willebrand Factor