Sandbox Reserved 1661: Difference between revisions
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Anaïs Kembou (talk | contribs) No edit summary |
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The second isoform was found in blood circulation and lost the amino acids 32 till 46 due to alternative splicing of the pre-mRNA and therefore has a molecular weight of 20 kDa. It has a reduced insulin linked activity but is still very similiar to the predominant form, although a quarter of the amino acids in the long loop between helices 1 and 2 was deleted. The loss of these amino acids could be compensated due to the flexibility of the loop region. Through the lack of Lys41, the isoform can not form a saltbridge between hGH and the first receptor. It is possible for the hGH to compensate partially a deficit of 200Å contact surface area through Pro33 and Leu37 in hydrophobic interaction and Arg152 in salt bridge. The third isoform has a molecular weight of 17,5kDa and is formed by alternative splicing of the pre-mRNA. A mutation in the first and sixth basepair leads to a missplicing of the mRNA and loss of exon 3. The GH produced thus lacks amino acids 32 to 71. The entire connecting loop between helices 1 and 2 and the Cys53 which is required for the first disulphide bridge is missing. Some deleted amino acids are part of a hydrophobic core which is essential to fold the molecule normally. The molecule gets instabil, it can not refold properly. Additionally, the receptor can not bind to binding site 1 which leads to a huge loss in activity. <ref name="pubMed">PMID:17584122</ref> | The second isoform was found in blood circulation and lost the amino acids 32 till 46 due to alternative splicing of the pre-mRNA and therefore has a molecular weight of 20 kDa. It has a reduced insulin linked activity but is still very similiar to the predominant form, although a quarter of the amino acids in the long loop between helices 1 and 2 was deleted. The loss of these amino acids could be compensated due to the flexibility of the loop region. Through the lack of Lys41, the isoform can not form a saltbridge between hGH and the first receptor. It is possible for the hGH to compensate partially a deficit of 200Å contact surface area through Pro33 and Leu37 in hydrophobic interaction and Arg152 in salt bridge. The third isoform has a molecular weight of 17,5kDa and is formed by alternative splicing of the pre-mRNA. A mutation in the first and sixth basepair leads to a missplicing of the mRNA and loss of exon 3. The GH produced thus lacks amino acids 32 to 71. The entire connecting loop between helices 1 and 2 and the Cys53 which is required for the first disulphide bridge is missing. Some deleted amino acids are part of a hydrophobic core which is essential to fold the molecule normally. The molecule gets instabil, it can not refold properly. Additionally, the receptor can not bind to binding site 1 which leads to a huge loss in activity. <ref name="pubMed">PMID:17584122</ref> | ||
</StructureSection> | |||
== HGH receptors and interactions == | == HGH receptors and interactions == | ||
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Affected by gigantism pathology, individuals may have therapeutic radiation and therapeutic drug treatment or synthesis of inhibitors such as somatostatin,<ref name="bgh"/> which act as GH antagonists by binding to the receptor, thus preventing the GH to perform its functions. | Affected by gigantism pathology, individuals may have therapeutic radiation and therapeutic drug treatment or synthesis of inhibitors such as somatostatin,<ref name="bgh"/> which act as GH antagonists by binding to the receptor, thus preventing the GH to perform its functions. | ||
== References == | == References == | ||
<references/> | <references/> | ||
