When the researchers investigate the amino acids sequence of a protein they usually use bioinformatics tools to gain more information about it. This includes, among other things, motifs of known structural or functional significance inherent in the protein sequence. A motif is a set of amino acids with an essential and conserved sequence or a typical structural elements in the protein folding, that is conveyed in a protein sequence and accounts for a biochemical function, structural domain or activity of the protein (Figure 1). In both cases, either when the motif refers to a particular amino acid sequence or a set of contiguous secondary structure elements, it originates in a conserved amino acid sequence. Thus, motifs can be predicted based on the protein sequence only without actually determining the protein structure. Determining the three- dimensional structure of a protein is a time consuming, expensive and complicated process. Analyzing protein sequence using bioinformatics tools is a short, simple and reliable process that does not require special resources or laboratorial platforms.

Figure 1: The sequence and structure of protein motifs

One of the main methods of identifying protein motifs is to compare the sequence of the studied protein with a database of known motifs. Such comparisons can recognize regions in the sequence of the studied protein that are similar to database motifs. If sequence similarities are identified, the function and/or structure of the identified regions in the protein sequences can be inferred from those of the known motifs. The tool Prosite includes a search engine that compares the protein sequence with sequences in the database of structural and functional motifs, thereby enabling the identification of motifs in the protein, and defines the protein family it belongs to.

Goals

The goal of this task is to identify motifs in the CFTR protein sequence that are of structural and functional significance, and thus to learn about the role that these motifs play in its function as an ion channel in the cell membrane. Another goal is to learn how a DNA mutation in the gene affects the sequence, structure and function of the CFTR protein, meaning, the relationship of genotype (the gene mutation) and phenotype (disease).

Prosite will assist us with:

  1. Identifying motifs in the CFTR protein that are important for its structure and function as an ion channel.
  2. Studying how CFTR gene mutations affect structural and functional protein motifs.