Protein function depends on three dimensional arrangements of amino acids and three dimensional structures depend on:
1. Length of amino acid: more length of amino acid, more folds will be in a structure.
2. Order of amino acid: arrangement of amino acid determines that how amino acids are folded e.g. hydrophobic amino acids (outside the amino acid, present in a membrane).
3. Types of amino acid present in a particular peptide: types include alpha or beta which determines the structure of proteins.
If we have a denovo protein and we want to find its function, through Bioinformatics Tools we can determine the sequence of protein. We determine if two sequences are same its structure will be same and structure determines the function of protein.
Evolutionary relationship between proteins
On the basis of sequence similarities we make protein families. Mapping of evolutionary relationship means identifying protein family. We can determine protein through evolutionary history that which family protein belongs to.
Homolog: the protein having same ancestor.
Paralog: the protein that arises due to gene duplication within a genome, they evolve new functions, if they are related to the original one.
Ortholog: are genes in different species that evolved from common ancestor gene by speciation, they retain same function in the course of evolution.
Suppose we have an ancestor protein called "globin" (the oxygen carrying compound in red blood cells). Due to gene duplication ß-globin and myoglobin (paralogs) arisen during DNA replication. ß-globin and myoglobin are present in human and mouse evolved from same ancestor (orthologs).
• ß-globin of mouse is paralogs to myoglobin of human, but function slightly varies.
• ß-globin of mouse are orthologs to ß-globin of humans,i.e. same function due to conserved region.
Domains are functional unit of proteins. During evolution they are conserved. If two proteins have same function, they have same domains.
Suppose we have an enzyme TPA, Tissue Plasminogen Activator, it has four domains.
Domain 1: Fibronectin type II (FnII)
Interaction with fibrin (blood clotting agent)
Domain 2: Epidermal growth factor (EGF)
Promotes cell division.
Domain 3: Kringle
Interacts with fibrin.
Domain 4: Serine protease
It cleaves protein.
How these domains are arranges?
Due to rearrangement of exons sequence varies.
The FnII domain in tissue plasminogen activator is adjacent to EGF domain whereas in factor XII the FnII domain is sandwiched between two EGF domains.
In Urokinase (homeostatic protein) FnII domain does not exist, whereas it contains EGF and kringle domain.
If proteins are orthologs, it is easy to determine its function through databases for example, polar bear and human globin. But it is very difficult to determine function of proteins which are paralogs. We can conclude biological functions.
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