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PROSITE documentation PDOC00912 |
The structures of transforming growth factor-β (TGF-β), nerve growth factor (NGF), platelet-derived growth factor (PDGF) and gonadotropin have been shown to be similar [1,2 and references therein]: these proteins are folded into two highly twisted antiparallel pairs of β-strands and contain three disulfide bonds, of which two form a cystine ring through which the third bond passes (see the schematic representation below). This structure is called cystine knot [3].
+--<======b3======C---c------+ | : : | +--==c====b4===>C-:-C-c-COOH | : : : : | +--==c====b2===>C---C--------+ | : +--<======b1======C--------------NH(2)
'=>': indicates the direction of the beta-strands 'b1' to 'b4'. 'C' : conserved cysteine in cystine knot. 'c' : additional conserved cysteine in C-terminal cystine knot. ':' : disulfide bridge.
Functional diverse modular proteins share a conserved domain of about 90 amino acids in their C-terminal cysteine-rich region, that has been proposed [4,5] to be structurally related to the cystine-knot family [3] and which is therefore called C-terminal cystine-knot (CTCK). Members of the C-terminal cystine knot family are listed below:
The pattern we developed for CTCK correspond to the C-terminal half of the domain.
Expert(s) to contact by email: Last update:May 2004 / Text revised.
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PROSITE methods (with tools and information) covered by this documentation:
1 | Authors | Isaaks N.W. |
Source | Curr. Opin. Struct. Biol. 5:391-395(1995). |
2 | Authors | Sun P.D. Davies D.R. |
Title | The cystine-knot growth-factor superfamily. | |
Source | Annu. Rev. Biophys. Biomol. Struct. 24:269-291(1995). | |
PubMed ID | 7663117 |
3 | Authors | McDonald N.Q. Hendrickson W.A. |
Title | A structural superfamily of growth factors containing a cystine knot motif. | |
Source | Cell 73:421-424(1993). | |
PubMed ID | 8490958 |
4 | Authors | Meitinger T. Meindl A. Bork P. Rost B. Sander C. Haasemann M. Murken J. |
Title | Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure. | |
Source | Nat. Genet. 5:376-380(1993). | |
PubMed ID | 8298646 | |
DOI | 10.1038/ng1293-376 |
5 | Authors | Bork P. |
Title | The modular architecture of a new family of growth regulators related to connective tissue growth factor. | |
Source | FEBS Lett. 327:125-130(1993). | |
PubMed ID | 7687569 |