Sandbox Reserved 1661: Difference between revisions
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Binding to the receptor is the first step in the biological action of the hormone.<ref name="m/s"/> For the binding of a single HGH, two HGH receptors are needed. The HGH binds with its high affinity binding site 1 onto the extracellular domain of the first receptor and with the low affinity binding site 2 onto the extracellular domain of the second receptor <ref name="pubMed">PMID:17584122</ref>. This leads to receptor homodimerization and transmits the signal into the target cell. | Binding to the receptor is the first step in the biological action of the hormone.<ref name="m/s"/> For the binding of a single HGH, two HGH receptors are needed. The HGH binds with its high affinity binding site 1 onto the extracellular domain of the first receptor and with the low affinity binding site 2 onto the extracellular domain of the second receptor <ref name="pubMed">PMID:17584122</ref>. This leads to receptor homodimerization and transmits the signal into the target cell. | ||
The first binding site of the HGH protein contains parts of helices 1 and 4, as well as parts of the binding loop between helices 1 and 2. The second binding site contains the N-terminus and part of the third helix. Major roles hereby play Phenylalanine 1 and Isoleucine 4 (N-terminus) and Aspartic acid 116. The C-terminal part of the receptor, consisting of the last 165 amino acids, has no effect on GH binding.<ref name="m/s"/> | The first binding site of the HGH protein contains parts of helices 1 and 4, as well as parts of the binding loop between helices 1 and 2. The second binding site contains the N-terminus and part of the third helix. Major roles hereby play Phenylalanine 1 and Isoleucine 4 (N-terminus) and Aspartic acid 116. The C-terminal part of the receptor, consisting of the last 165 amino acids, has no effect on GH binding.<ref name="m/s"/> | ||
Several GH variants with modified N-terminus were explored to learn more about the behaviour of the binding of the receptor molecule. A GH with an extension of Methionin on the N-terminus behave identical to an authentic GH in assays. The small, neutral amino acid without any side chains has no apparent effect on the binding of the receptor. In contrast, a removal of 13 amino acids at the N-terminus results in reduced binding activity to somatogenic receptors and decreased biological activity, because the amino acids 1 to 16 are involved in the binding site 2. But the other part of the binding site (with Trp103, Asp116 and Glu119 from helix 3) of the hGH molecule are intact and available for binding of the receptor. The N-terminus is required for full biological activity, however, additions still deletions can not completly abolish the functions of the molecule. | |||
The hormone-binding extracellular domain consists of 250 amino acids, including several cysteine residues which are conserved and can form disulphide bridges.The intracellular domain of the receptor is made up of 350 amino acids, it represents the least conserved region and is made up of 10 tyrosine residues likely to be phosphorylated by tyrosine kinase (JAK2), during the formation of the GH-receptor complex. A reaction cascade involving kinase enzymes is then activated, allowing the expression of certain genes coding for proteins or not, necessary for biological activity. It therefore controls the expression of certain genes such as the gene coding for the IGF-1 factor. The liver and adipose tissue being important targets for GH, it therefore contributes to metabolic homeostasis.<ref name="m/s"/> | The hormone-binding extracellular domain consists of 250 amino acids, including several cysteine residues which are conserved and can form disulphide bridges.The intracellular domain of the receptor is made up of 350 amino acids, it represents the least conserved region and is made up of 10 tyrosine residues likely to be phosphorylated by tyrosine kinase (JAK2), during the formation of the GH-receptor complex. A reaction cascade involving kinase enzymes is then activated, allowing the expression of certain genes coding for proteins or not, necessary for biological activity. It therefore controls the expression of certain genes such as the gene coding for the IGF-1 factor. The liver and adipose tissue being important targets for GH, it therefore contributes to metabolic homeostasis.<ref name="m/s"/> | ||
