Sandbox Reserved 1661: Difference between revisions

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 [https://edoc.ub.uni-muenchen.de/8706/1/Burget_Lukas.pdf]. 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 lacks amino acids 32 to 71 and causes isolated GH deficiency type II. The entire connecting loop between helices 1 and 2 and the Cys53 which is required for the first disulphide bridge is missing which leads to unpaired cysteine. 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> <ref name="Endokrynologika Polska">DOI:10.5603/EP.2013.0009</ref>

== HGH receptors and interactions  ==