The Functional Significance of Protein Sequence Signatures

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Adenosine triphosphate (ATP) binding cassette (ABC) transporters are transmembrane proteins which function to transport many substrates across membranes and ensure the fidelity of transcription and translation in an ATP dependent manner (Jones & George, 2004). These transporters can carry out their functions as there are information contained within molecular sequences that define their roles. Such information are usually in the form of motifs and are located at certain regions of their respective molecular sequences known as domains. These motifs are usually conserved (Bork & Koonin, 1996) and such an understanding becomes important in many areas of research. One of the research interests involves the development of novel treatments against the multi-drug resistant property of ABC transporters in treating relevant human diseases such as cystic fibrosis and Tangier disease (Stefková et al., 2004). With any of such novel applications, a substantial knowledge on sequence motifs in terms of their functional significance is required. In this essay, the discussion is limited to protein sequence signatures in nucleotide binding domains (NBDs) of ABC transporters relating to substrate translocation. It will be seen that the protein sequence motifs perform similar function across species, and any mutation can affect its overall function. However, it should also be noted that these motifs can result in slightly different mechanism in different species, and that they can perform their function at certain domains of the protein. The understanding of protein sequence signatures has to be first introduced before assessing their functional significance. Protein sequences are one dimensional string of amino acid letter codes that represent the ... ... middle of paper ... B motif in the N-terminal nucleotide binding domain (NBD-1) of Cdr1p of Candida albicans has acquired a new role in ATP hydrolysis. Biochemistry, 45(49): 14726. Schmees, G., Stein, A., Hunke, S., Landmesser, H., & Schneider, E. (1999). Functional consequences of mutations in the conserved 'signature sequence' of the ATP-binding-cassette protein MalK. Eur J Biochem, 266(2): 420-430. Stefková, J., Poledne, R., & Hubácek, J. A. (2004). ATP-binding cassette (ABC) transporters in human metabolism and diseases. Physiological research / Academia Scientiarum Bohemoslovaca, 53(3): 235. Tanabe, K., Lamping, E., Nagi, M., Okawada, A., Holmes, A. R., Miyazaki, Y., Cannon, R. D., Monk, B. C., & Niimi, M. (2011). Chimeras of Candida albicans Cdr1p and Cdr2p reveal features of pleiotropic drug resistance transporter structure and function. Molecular microbiology, 82(2): 416-433.
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