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The RAG complex protein is composed of two subunits, RAG-1 and RAG-2. RAG-1 and RAG-2 are critical in T and B cell maturation, promoting an adaptive immune response.

Function

This RAG complex protein allows the human body to have diverse immune response. Using both RAG-1 and RAG-2 together allows for recombination to occur to create cell receptors on both B and T cells. It is critical that the cell receptors are diverse in order to recognize a wide variety of pathogens and protect the body. RAG-1 and RAG-2 appear in the body as a complex. Both RAG-1 and RAG-2 are necessary for the function of the protein. RAG-1 cannot perform all of the functions by itself associated with the RAG protein; similarly, RAG-2 cannot perform all of the functions alone. The RAG-1 protein will bind to a specific recombination signal sequence within the V-J region of the light chain and the D-J segment along with the V-DJ segment of a heavy chain. Next, RAG-1 will bring the various segments within close proximity, looping the DNA between the segments out. RAG-2 will then cut the RSS sequence and a different protein will bind the two DNA ends.

Disease

Relevance

This protein is predominantly important during the B and T cell development. Because humans need to be well-protected from antigens, B cells and T cells must have a variety of proteins on their surface in order to recognize a variety of invaders. Causing these proteins to become diverse involves a series of segments known as Variable (V), Diversity (D), and Joining (J) segments. These segments can be arranged in many combinations of sequences that ensure variable surface proteins. Without the RAG protein, B and T cells would lack the ability to identify and destroy foreign pathogens

Structural highlights

found in RAG complex.

is the dimerization formation of RAG-1. It features four zinc binding-motifs that assist in RAG1 binding to the specific recombination signal sequence.

is the asymmetrical crystal structure of RAG1, featuring the dimer bound to a DNA molecule. In reality, the dimer binds two DNA molecules, one bound in a cis configuration and the other bound in trans configuration.

contains a plant homeodomain (PHD) near its C terminus (RAG2-PHD). This is unique because when a peptide is not being modified, a peptide N-terminal occupies the binding site, meaning that it is self-regulated. There is significantly less structural data on RAG2 due to a debate about the function of RAG2. Many challenge the belief that RAG2 cuts the RSS sequence, believing instead that RAG2 acts as a regulatory component to the complex.