This page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.

Protein Domains





Figure 1. Domains of the GRM7 isoform a protein. 
The GRM7 isoform a protein has three primary domians, including an ANF receptor (Receptor family ligand binding region) (shown in
green), an NCD3G (Nine Cysteines Domain of family 3 G-protein coupled receptor) (shown in red), and a 7tm_3 (7 transmembrane sweet-taste receptor of 3 G-protein coupled receptor) (shown in yellow) (Finn, et al., 2008).


To determine the domains of the human GRM7 isoform a protein, the protein sequence was searched against Pfam protein domain database and the SMART database. Both of these sites showed that the GRM7 protein contained three large domains, including an ANF receptor (Receptor family ligand binding region) domain, an NCD3G (Nine Cysteines Domain of family 3 G-protein coupled receptor) domain, and a 7tm_3 (7 transmembrane sweet-taste receptor of 3 G-protein coupled receptor) domain (Finn, et al., 2008; Letunic, et al. 2009; Schultz, et al., 1998). The SMART database also showed that the GRM7 protein has a low complexity domain near its N-terminus as well as six transmembrane domains within the 7tm_3 domain (Letunic, et al. 2009; Schultz, et al., 1998). The GRM7 protein sequence was also searched against the PROSITE database; however, as only the 7tm_3 domain was returned, the results from this website were not helpful in elucidating domains of the GRM7 protein (Hulo, et al., 2007).

The ANF receptor domain belongs to a family of extracellular ligand binding domains and is most likely the domain though which the GRM7 protein binds the neurotransmitter glutamate (
Finn, et al., 2008; Kuryatov, et al., 1994). The NCD3G domain of the GRM7 protein, which is also extracellular, contains several cystine residues and is predicted to consist of several disulphide bridges (Finn, et al., 2008). The function of these disulfide bridges may be to provide a stable link between the ANF receptor domain and the 7tm_3 domain. The transmembrane portion of the GRM7 protein is formed by the 7tm_3 domain, which contains seven transmembrane regions (six of which were identified using the SMART database) (Finn, et al., 2008;
Letunic, et al. 2009; Schultz, et al., 1998). This domain gets its name because the seven transmembrane regions form a docking pocket to which molecules like cyclamate and lactisole can bind, and thereby, confer the taste of sweetness (Jiang, et al., 2005). This domain is likely to be involved in transmitting the glutamate signal to the cell cytoplasm.

References

References

 

Finn, R.D, Tate, J., Mistry, J., Coggill, P. C., Sammut, J. S., Hotz, H. R., Ceric, G., Forslund, K., Eddy, S. R., Sonnhammer, E. L., and Bateman, A. (2008). The Pfam protein families database. Nucleic Acids Research. 36(Database issue):D281-D288.

Hulo N., Bairoch A., Bulliard V., Cerutti L., Cuche B., De Castro E., Lachaize C., Langendijk-Genevaux P.S., Sigrist C.J.A. (2007). The 20 years of PROSITE. Nucleic Acids Res. 1-5. doi:10.1093/nar/gkm977

Kuryatov, A., Laube, B., Betz, H., Kuhse, J. (1994). Mutational analysis of the glycine-binding site of the NMDA receptor: structural similarity with bacterial amino acid-binding proteins. Neuron 12:1291-1300.

Jiang, P., Cui, M., Zhao, B., Snyder. L.A., Benard, L.M., Osman, R., Max, M., Margolskee, R.F. (2005) Identification of the cyclamate interaction site within the transmembrane domain of the human sweet taste receptor subunit T1R3. J Biol Chem. 280:34296-34305.

Letunic I, Doerks T, Bork P. (2009). SMART 6: recent updates and new developments. Nucleic Acids Res. 37(Database issue):D229-32. doi:10.1093/nar/gkn808

Schultz, J., Milpetz, F., Bork, P. & Ponting, C.P. (1998). SMART, a simple modular architecture research tool: Identification of signaling domains. PNAS 95: 5857-5864.

Jennifer Wagner
wagner4@wisc.edu
Updated February 28, 2009
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