Sandbox Reserved 1661: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 8: | Line 8: | ||
== Structure == | == Structure == | ||
<Structure load='1hgu' size='350' frame='true' align='right' caption='Representation of the 3D structure of somatotropin' scene='Insert optional scene name here' /> | <Structure load='1hgu' size='350' frame='true' align='right' caption='Representation of the 3D structure of somatotropin' scene='Insert optional scene name here' /> | ||
Somatotropin has three major isoforms. The predominant form is composed out of 191 amino acids and has a molecular weight of 22 kDa. | Somatotropin has three major isoforms. The predominant form is composed out of 191 amino acids and has a molecular weight of 22 kDa. | ||
The '''primary structure''', corresponding to a sequence of amino acids, of the predominant somatotropin is the following : | The '''primary structure''', corresponding to a sequence of amino acids, of the predominant somatotropin is the following : | ||
PUT IMAGE | PUT IMAGE | ||
| Line 17: | Line 15: | ||
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. | The protein has two different binding sites: both located at the ends of the protein, the N-terminus as well as the C-terminus. | ||
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. | |||
A large number of reports are published on structre-function relationship of GH using chemical modifications, proteolytic digestion or molecular biological methods to alter or delete amino acids or regions. Mutations in the structure lead often to alterations of the binding characteristics due to the effects on protein confirmation. | A large number of reports are published on structre-function relationship of GH using chemical modifications, proteolytic digestion or molecular biological methods to alter or delete amino acids or regions. Mutations in the structure lead often to alterations of the binding characteristics due to the effects on protein confirmation. | ||
