Sandbox Reserved 1661
From Proteopedia
| Line 4: | Line 4: | ||
== Somatotropin and Genetic origin == | == Somatotropin and Genetic origin == | ||
| - | Somatotropin is a polypeptide hormone produced by the somatotropic cells of the pituitary gland. Growth hormone, a protein circulating in the blood. | + | Somatotropin (GH for ''Growth Hormone'' or HGH for ''Human Growth Hormane'') is a polypeptide hormone produced by the somatotropic cells of the pituitary gland. Growth hormone, a protein circulating in the blood. |
The Human Growth Hormone has its origin on chromosome 17. There it gets encoded by the Growth hormone 1 gene along with four other related genes. Three of these genes are encoding human chorionic somatomammotropin, which is closely related to somatotropin. They are all in the same transcriptional orientation. | The Human Growth Hormone has its origin on chromosome 17. There it gets encoded by the Growth hormone 1 gene along with four other related genes. Three of these genes are encoding human chorionic somatomammotropin, which is closely related to somatotropin. They are all in the same transcriptional orientation. | ||
| Line 18: | Line 18: | ||
PUT IMAGE | PUT IMAGE | ||
| - | Somatotropin does not exist as a linear chain of amino acids | + | Somatotropin does not exist as a linear chain of amino acids, it twists and folds on itself, forming the '''secondary structure'''. The protein consists of four antiparallel aligned α-helices. The first helix starts at the 6th amino acid, which is a leucine and ends with the 37th amino acid proline. It is separated from the other three helices after the 37th position. The 38th and 39th amino acids, which are lysine and glutamic acid are spliced out of the protein and therefore disconnects the first helix from the second one. The second helix starts at position 72 till 92, the third from 106 till 128 and the fourth helix from 155 until 184. |
| - | From the secondary structure, we obtain the tertiary structure, which corresponds to the 3D structure adopted by all the alpha helixes. The structural maintenance is ensured by electrostatic, hydrophobic, hydrogen and/or covalent interactions with cysteine 53 and cysteine 165 that form a disulphide bridge as well as cysteine 182 with cysteine 189. | + | From the secondary structure, we obtain the '''tertiary structure''', which corresponds to the 3D structure adopted by all the alpha helixes. The structural maintenance is ensured by electrostatic, hydrophobic, hydrogen and/or covalent interactions with cysteine 53 and cysteine 165 that form a disulphide bridge as well as cysteine 182 with cysteine 189. |
The protein has two different binding sites: both located at the ends of the protein, the N-terminus as well as the C-terminus.3 | The protein has two different binding sites: both located at the ends of the protein, the N-terminus as well as the C-terminus.3 | ||
| - | == | + | == HGH receptors and interactions == |
| + | The gene coding for the GH receptor is located on chromosome 5, it contains 9 exon and 87 kb. The complementary DNA, synthesised from an mRNA, representing the coding part of the genome, has been transcribed during reverse transcription and therefore contains only the exons. This DNA codes for a 626 amino acid protein containing the signal peptide, an extracellular domain highly conserved, an hydrophobic transmembrane domain, and a variable intracellular domain. | ||
| + | The GH membrane receptor is found on many cells and tissues with the exception of the brain, testicles and thymus.The nature of this receptor is not fully understood, but it seems that it may be present in different forms due to different post-translational changes that may occur in a single protein <ref name= »m/s»> Le Cam, A. (1993), Mode d’action de l’hormone de croissance. médecine/sciences, 12 :1352-61.</ref>. | ||
| + | |||
| + | The HGH receptor is a transmembrane protein consisting of 620 amino acids. It has two extracellular domains, each containing 7 β-sheets. The protein should theoretically have a molecular mass of 70 kDa considering the amino acid sequence. In fact the actual molecular weight is 100 - 130 kDa. This can be explained due to post-translational modifications such as glycosylation and ubiquitination. Ligand binding increases ubiquitination and possibly has effect on GH receptor internalisation. | ||
| + | |||
| + | Binding to the receptor is the first step in the biological action of the hormone <ref name="m/s"</ref>. For the binding of a single HGH, two HGH receptors are needed. The HGH binds with one of its binding sites onto the extracellular domain of the first receptor and with the other binding site onto the extracellular domain of the second receptor. 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 part 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"</ref>. | ||
| + | |||
| + | 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"</ref>. | ||
| + | |||
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | ||
Revision as of 20:30, 13 January 2021
/>
| This Sandbox is Reserved from 26/11/2020, through 26/11/2021 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1643 through Sandbox Reserved 1664. |
To get started:
More help: Help:Editing |
Contents |
Somatotropin and Genetic origin
Somatotropin (GH for Growth Hormone or HGH for Human Growth Hormane) is a polypeptide hormone produced by the somatotropic cells of the pituitary gland. Growth hormone, a protein circulating in the blood. The Human Growth Hormone has its origin on chromosome 17. There it gets encoded by the Growth hormone 1 gene along with four other related genes. Three of these genes are encoding human chorionic somatomammotropin, which is closely related to somatotropin. They are all in the same transcriptional orientation.
Functions
Somatropin plays an important role in physiological environments such as: increasing muscle mass, reducing fat mass, providing the energy necessary for tissue growth, maintaining the right level of glucose and lipids ... and the development of the individual's body [1]. It acts directly on a cell surface or indirectly [1]. In the second case, somatropin stimulates tissues such as the liver, which in turn allows the synthesis and secretion of IGF-1, thus enabling the development of cell growth, tissue, bone and thus the linear growth of the individual [2].
Structure
|
Somatotropin has two major isoforms. The predominant form is composed out of 191 amino acids and has a molecular weight of 22 kDa. The second isoform lost amino acids 32 till 46 due to alternative splicing of the pre-mRNA and therefore has a molecular weight of 20 kDa.
The primary structure, corresponding to a sequence of amino acids, of the predominant somatotropin is the following : PUT IMAGE
Somatotropin does not exist as a linear chain of amino acids, it twists and folds on itself, forming the secondary structure. The protein consists of four antiparallel aligned α-helices. The first helix starts at the 6th amino acid, which is a leucine and ends with the 37th amino acid proline. It is separated from the other three helices after the 37th position. The 38th and 39th amino acids, which are lysine and glutamic acid are spliced out of the protein and therefore disconnects the first helix from the second one. The second helix starts at position 72 till 92, the third from 106 till 128 and the fourth helix from 155 until 184. From the secondary structure, we obtain the tertiary structure, which corresponds to the 3D structure adopted by all the alpha helixes. The structural maintenance is ensured by electrostatic, hydrophobic, hydrogen and/or covalent interactions with cysteine 53 and cysteine 165 that form a disulphide bridge as well as cysteine 182 with cysteine 189. The protein has two different binding sites: both located at the ends of the protein, the N-terminus as well as the C-terminus.3
HGH receptors and interactions
The gene coding for the GH receptor is located on chromosome 5, it contains 9 exon and 87 kb. The complementary DNA, synthesised from an mRNA, representing the coding part of the genome, has been transcribed during reverse transcription and therefore contains only the exons. This DNA codes for a 626 amino acid protein containing the signal peptide, an extracellular domain highly conserved, an hydrophobic transmembrane domain, and a variable intracellular domain. The GH membrane receptor is found on many cells and tissues with the exception of the brain, testicles and thymus.The nature of this receptor is not fully understood, but it seems that it may be present in different forms due to different post-translational changes that may occur in a single protein [3].
The HGH receptor is a transmembrane protein consisting of 620 amino acids. It has two extracellular domains, each containing 7 β-sheets. The protein should theoretically have a molecular mass of 70 kDa considering the amino acid sequence. In fact the actual molecular weight is 100 - 130 kDa. This can be explained due to post-translational modifications such as glycosylation and ubiquitination. Ligand binding increases ubiquitination and possibly has effect on GH receptor internalisation.
Binding to the receptor is the first step in the biological action of the hormone [4].
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 [5]
