Conservation of Protein Domains Over Different Proteins

A protein domain is a self-contained section of a protein that is capable of independently folding into its three-dimensional structure.  There are limited ways protein domains can fold since certain specific three-dimensional arrangements of alpha helices, beta sheets, and loops are more energetically favorable than others.  There are tens of thousands of different proteins, but there are less than 1500 known domains because similar domains appear in many proteins. Proteins with short amino acid sequences will likely have only one domain, but the majority of proteins contain multiple domains with distinct functions. The multiple domains of a protein work together to allow it to perform its role, and often one domain acts to regulate the function of another domain. For example, when a ligand binds to the ligand-binding domain of a receptor – this can trigger the enzymatic function of the catalytic domain to be enhanced. The protein domains have evolved as modules that can be rearranged to create new proteins with unique functions in a process called domain shuffling. These units will combine in different orientations depending on the location of the N- and C-terminal tails of the amino acid chain.  If the N terminus and C terminus of the domain are in close proximity, the protein will end up as a compact globular structure, while if the N and C termini are on opposite ends of the domain, the overall structure will end up elongated linear. Src is a protein containing three distinct protein domains. Two of these domains, called the Src Homology domains SH2 and SH3 allow proteins containing this domain to bind to specific sequences of amino acid chains. Each of these domains is conserved across different proteins. The SH2 domain binds to phosphorylated tyrosines and is found in over 115 different proteins.  The SH3 domain binds to proline-rich sequences and is found 300 times in the human genome.   These protein domains and others are genetic building blocks for creating proteins that combine multiple functions in unique ways.