Assignment 2 - Leptin Structure

Figure 1: Crystal Structure of Leptin. (Taken from NCBI website).

The human leptin gene is just over 16,000 base pairs in length, and is located on chromosome 7, at 7q31.3 (NCBI). It encodes a 16 kDa, 167 amino acid protein with four antiparallel alpha helices, similar to the long-chain helical cytokine family of proteins (Zhang et al., 2007). The tertiary structure of the protein includes a "hydrophobic core" of amino acids facing inward on each helix, and a disulphide bond between cysteine residues 96 and 146. This disulphide bond is particularly important to folding of the protein and for binding the leptin receptor (Fruhbeck, 2006). As seen in the protein alignment below, Cys96 and Cys146 are conserved between species as varied as human, chicken and sturgeon. Sections of the four alpha helices are also well conserved between species (Zhang et al., 2007).

Figure 1: Alignment of protein sequences for Mus musculus leptin

 (Accession number NM_008493), Gallus gallus leptin (AF012727), Acipenser

 schrenckii leptin (DQ784816) and Homo sapiens leptin (U43653). Prepared using

 ClustalW software.

 

The scores associated with this alignment indicate that the most similar sequences are those from the mouse and sturgeon, while the human sequence is least similar to any of the others.

Table 1: Alignment Scores for Mouse, Human, Chicken and Sturgeon

Leptin Protein Sequences

SeqA Name       Len(aa)  SeqB Name       Len(aa)  Score

=======================================================

1    mouse      167      2    human      167      83   

1    mouse      167      3    chicken    163      96   

1    mouse      167      4    sturgeon   146      99   

2    human      167      3    chicken    163      80   

2    human      167      4    sturgeon   146      84   

3    chicken    163      4    sturgeon   146      95   

=======================================================