Second Assignment

Structure of my favorite hormone: Neuropeptide F


Mature NPF in invertebrates is 362 base pairs long, the precursor is comprised of a "signal peptide followed by the mature peptide of 36 amino acids in length" (Dougan, P.M., et. al., 2002). NPF is a homologue of NPY in vertebrates, NPY in Homo sapiens is 37 amino acids in length (Dougan, P.M., et. al., 2002). One important difference in the structure of NPF and NPY is that NPF has a phenylalanine (Phe) residue at the C-terminus, whereas NPY has a Tyrosine (Tyr) (Lee, K., et. al, 2004).
The typical receptor for these peptides is the G-protein receptor, which are transmembrane receptors, the peptide will bind to the receptor on the cell surface and send signals via signal transduction.
Structure more often than not equals function, meaning the protein will not function properly if the structure is altered. We can assume that any conserved areas of the protein alignment (figure 1) will be the important active areas of the protein. They may be crucial for binding to the receptor or any other activity of the peptide.

Fig.1: Alignment of proteins for Fruit fly NPF (Genebank accession number NM_080493), silkworm NPF (accession number NM_001130883), Human NPY (accession number H15789) and goldfish NPY (accession number M87297). Click on the image for a larger image. Alignments were made using ClustalW software 
KEY: 

"*" means that the residues or nucleotides in that column are identical in all sequences in the alignment. 

":" means that conserved substitutions have been observed, according to the COLOUR table above. 

"." means that semi-conserved substitutions are observed.

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

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1    fly.npf        101      2    silkworm.npf   82       28  

1    fly.npf        101      3    human.npy      97       14  

1    fly.npf        101      4    goldfish.npy   96       15  

2    silkworm.npf   82       3    human.npy      97       20  

2    silkworm.npf   82       4    goldfish.npy   96       18  

3    human.npy      97       4    goldfish.npy   96       62  

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Table 1.0: Percent similarity based on protein alignment, between NPY and NPF of the species: Drosophila melanogaster, Bombyx mori, Homo sapien, & Carassius auratus.


You can see in Table 1.0 that Human NPY and Goldfish NPY are the highest conserved peptides.


References:

(1) Dougan, P.M., Mair, G.R., Halton, D.W., Curry, W.J., Day, T.A., & Maule, A.G. (2002). Gene Organization and Expression of a Neuropeptide Y Homolog from the Land Planarian Arthurdendyus triangulates. The journal of comparative neurology. 454;58-64.

(2) Lee, K., You, K., Choo, J., Han, Y., & Yu, K. (2004). Drosophila Short Neuropeptide F regulates food intake and body size. The Journal of Biological Chemistry. 279(49); 50781-50789.

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First Assignment

My Favorite Hormone: Neuropeptide F (NPF)


NPF is a 36 amino acid peptide in Drosophila Melanogaster, or fruit flies, that was found to be a homologue of the mammalian Neuropeptide Y hormone (Lee, K., et. al, 2004). NPY is synthesized and secreted by neurons into the peripheral nervous system and central nervous system. It can also be synthesized and secreted from islet cells of the pancreas, and via its Y1 receptor, it inhibits insulin secretion due to glucose. NPY has also been shown to be a potent stimulator in rodents in terms of food intake (Kronenberg, H.M., et. al, 2008). One important difference in the structure of NPF and NPY is that NPF has a Phenylalanine (Phe) residue at the C-terminus, whereas NPY has a Tyrosine (Tyr).
NPF has many diverse functions and affects many important processes in Drosophila, such as: behaviour, alcohol sensitivity, energy homeostasis, circadian rhythm, food intake, body size, reproduction, anxiety, seizure, learning and memory (Lee, G., et. al, 2006). 
NPF has a receptor known as NPFR1, which is linked to ethanol sedation. If there is a deficiency in NPF or this receptor, it has been shown that there is also a decrease in alcohol sensitivity. The opposite phenotype can be observed when there is overexpression of NPF or NPFR1 (Wen, T., et. al, 2005).
This same receptor, NPFR1, is linked to food intake as well. The activity of this receptor is mandatory for fasting larvae to participate in what is known as "cold-resistant feeding behaviour" (Lingo, P., et. al, 2007). In other words, these fasted larvae would not eat cold food if their lives depended on it, unless this receptor was active. From this study, it can be suggested that the mammalian NPF-like system (NPY) can play a central role in gustation.

References:

1)      Kronenberg, H.M., Melmed, S., Polonsky, K.S., & Larsen, P.R. (2008). Williams Textbook of Endocrinology. 1955. Reprint. Philadelphia, PA: Saunders Elsevier.

2)      Lee, G., Bahn, J.H., & Park, J.H. (2006). Sex- and clock-controlled expression of the neuropeptide F gene in Drosophila. PNAS. 103(33); 12580-12585.

3)      Lee, K., You, K., Choo, J., Han, Y., & Yu, K. (2004). Drosophila Short Neuropeptide F regulates food intake and body size. The Journal of Biological Chemistry. 279(49); 50781-50789.

4)      Lingo, P., Zhao, Z., & Shen, P. (2007). Co-regulation of Cold-Resistant Food Acquisition by Insulin- and Neuropeptide Y-like Systems in Drosophila melanogaster. Neuroscience. 148(2); 371-374.

5)      Wen, T., Parrish, C., Wu, D., & Shen, P. (2005). Drosophila neuropeptide F and its receptor, NPFR1, define a signaling pathway that acutely modulates alcohol sensitivity. PNAS. 102(6); 2141-2146.