Tuesday, October 26, 2010

The Structure of my Least favorite Hormone: Relaxin


Relaxin is a 7 peptide hormone that is part of the insulin/IGF family. Similar to insulin, the active form of relaxin consists of two chains, linked by disulfide bridges. Studies show that no particular amino acid on the NH terminal region of the A chain is functionally important, but it is the presence of a helix that is required for biological activity (Erika et al.,1987).

RXFP1, RXFP2, RXFP3 and RXFP4 are the four receptors associated with Relaxin in humans (because I am finding it very hard to find information on this hormone with respect to other mammals). These are transmembrane G Protein coupled receptors. These glycosylated heptahelical domains are somewhat similar to FSH and LH receptors (shpakova, 2009).













Figure 1: Structural representation of Relaxin

Obtained from http://upload.wikimedia.org/wikipedia/commons/c/ce/Relaxin.png

To compare the similarity of Relaxin between species of Equus caballus (horse), Sus Scrofa (wild boar) and Felis catus (domestic cat), a sequence alignment was performed in ClustalW2, results are shown in the figure below.




Equus           -------------------------------IKACGRELARLRIEICGSLSWKKTVLRLE 29
Sus             MPRLFS-YLLGVWLLLSQLPREIPGQSTNDFIKACGRELVRLWVEICGSVSWGRTALSLE 59
Felis           MLRLFLSHLLGVWLLLSLRARKIP--AQEEVLKACGREFVRLQIRICGSLSWGKSSQQHR 58
                                               :******:.** :.****:** ::    .


Equus           EPGLEVGQPVEIVSSSISKDAEALNTKLGLNSNLPKEQKATLSERQPSWRELLQQPALKD 89
Sus             EPQLETGPPAETMPSSITKDAEILKMMLEFVPNLPQELKATLSERQPSLREL-QQSASKD 118
Felis           EPRQAPAALPEIVSSSITSGAEALNGMLEYIPDLPQELKATLSEREPSFREL--QPSLKD 116
                **    .   * :.***:..** *:  *   .:**:* *******:** ***  *.: **


Equus           SNLNLEEFEETIQKTQSEVEDDSLSELKNLGLDKHSRKKRMI--QLSHKCCYWGCT---- 143
Sus             SNLNFEEFKKIILNRQNEAEDKSLLELKNLGLDKHSRKKRLFRMTLSEKCCQVGCIRKDI 178
Felis           SNLNLEEVEKSILGRQNEAEDQSLSQLGRSRLDAHSRIKRSDYIRYSDRCCNVGCTRKEL 176
                ****:**.:: *   *.*.**.** :* .  ** *** **      *.:**  **    


Equus           ----
Sus             ARLC 182
Felis           ADLC 180

- * indicates identical residues
- :  indicates there are conserveral substitutions
- .  indicates substitutions are semi-conserved


The percent similarity between each species was compared, showing that the sequence is fairly conserved between species, between 56 and 66% similarity.

Table 1. Sequence similary of the hormone Relaxin between Equus caballus, Sus Scrofa (wild boar) and Felis Catus obtained in ClustalW2

SeqA Name    Len(aa)  SeqB Name    Len(aa)  Score
=================================================
1    Equus   143      2    Sus     182      66   
1    Equus   143      3    Felis   180      58   
2    Sus     182      3    Felis   180      56   
=================================================

References

Erika,E., Bullesbach, Christian,S. (1987) "Relaxin structure, quasi allosteric effect of the nhz-terminal a-chain helix" The American Society for Biochemistry and Molecular biology, 262(26)

Shpakov, Shpakova. (2009) "Low-molecular regulators of polypeptide hormone receptors containing LGR-repeats" Biomedical Chemistry 3(4); 351-360