The crystal structures of four growth factors; nerve growth factor, transforming growth factor-beta, platelet-derived growth factor, and human chorionic gonadotropin from four separate superfamilies revealed that these proteins are structurally related and share a common overall topology [ (PUBMED:8490958) ]. These proteins show very little sequence homology, but they all have an unusual arrangement of six cysteines linked to form a "cystine-knot" conformation. The active forms of these proteins are dimers, either homo- or heterodimers [ (PUBMED:7663117) ]. Because of their shape, there appears to be an intrinsic requirement for the cystine-knot growth factors to form dimers. This extra level of organisation increases the variety of structures built around this simple structural motif [ (PUBMED:7583638) ].
Glycoprotein hormones [ (PUBMED:6267989) (PUBMED:1445230) ] (or gonadotropins) are a family of proteins which include the mammalian hormones follitropin (FSH), lutropin (LSH), thyrotropin (TSH) and chorionic gonadotropin (CG), as well as at least two forms of fish gonadotropins. All these hormones consist of two glycosylated chains (alpha and beta). In mammalian gonadotropins, the alpha chain is identical in the four types of hormones but the beta chains, while homologous, are different.
The beta chains are proteins of about 100 to 140 amino acid residues which contain the cysteine-knot domain [ (PUBMED:8202136) ], as shown in the following schematic representation.
Crystal structure of human chorionic gonadotropin.
Nature. 1994; 369: 455-61
Display abstract
The three-dimensional structure of human chorionic gonadotropin shows that each of its two different subunits has a similar topology, with three disulphide bonds forming a cystine knot. This same folding motif is found in some protein growth factors. The heterodimer is stabilized by a segment of the beta-subunit which wraps around the alpha-subunit and is covalently linked like a seat belt by the disulphide Cys 26-Cys 110. This extraordinary feature appears to be essential not only for the association of these heterodimers but also for receptor binding by the glycoprotein hormones.
Structure--function relationships of the glycoprotein hormones and their receptors.
Trends Pharmacol Sci. 1991; 12: 199-203
Display abstract
The primary structures of the glycoprotein hormones follitropin (FSH), lutropin (LH), human choriogonadotropin (hCG) and thyrotropin (TSH) have been determined, hCG has been crystallized and initial diffraction data obtained. Studies with synthetic peptides have provided information on regions involved in receptor interaction and signal transduction. The receptors for the glycoprotein hormones have been prepared by gene cloning methods and their primary structures deduced. As Leo Reichert and colleagues discuss here, although cAMP is involved in glycoprotein hormone signal transduction, recent evidence also implicates other second messengers, especially Ca2+ and may include both the phosphatidylinositol pathway and activation of Ca2+ channels.
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with GHB domain which could be assigned to a KEGG orthologous group, and not all proteins containing GHB domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
