The Rag-1: The Human Immune System

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Introduction The human immune system consists of an immense amount of proteins, cells, and systems that all simultaneously work together to defend the body against any pathogens that come its way. One of these important proteins is the recombinase activating gene, Rag-1. Rag-1 plays a major part in lymphocyte production, and when this gene is knocked out, it can cause a major negative effect in the immune system. When Rag-1 is knocked out, the process in making T and B cell receptors is completely disabled. Because of this, all of the lymphocytes in a Rag-1 deficient organism are immature, and unable to participate in normal immune system functioning. Fortunately, there are no physical or neurological deformities in the organism because of …show more content…

The Rag-1 comes in different forms such as a dimer, tetramer, or octomer. The octomer is the most stable form in a not as strong ionic solution, but the most common form found in a biological environment is the dimer form. Each subunit of the Rag-1 protein contains many alpha helices also. The active site in Rag-1 is soluble, and it houses the most important and largest domains of the protein: the N-terminis domain, the C-terminis domain, and the core domain. A combination of these domains could perform all of the functions of the protein without the other residues. The N-terminis region and the core domain bind to RSS site at the nonomer region and the 12 or 23 spacer portion respectively. In binding to the RSS site, the core domain instigates a conformational change in the DNA which allows the complex to interact and cut the DNA appropriately. It is theorized that the Rag-1 gene along with its partner, Rag-2, were once a transposable element (Agrawal et al.). Scientists have found that the transposon containing these two genes was solidified into the genome once jaw containing vertebrates split from jawless vertebrates. From then on, the Rag genes have been in mammalian DNA, and have played a major part in their …show more content…

The Process of V(D)J Recombination a) The V, D, or J double-stranded DNA sequence is flanked by an RSS site. b) Rag-1 and Rag-2 bind simultaneously on the RSS joints. c) The Rag complex initiates a single stranded nick between the RSS and the coding region. d) Through an attack by the 3’ OH end, the DNA forms a hairpin leaving the RSS site with a double stranded break. e) With the help of accessory proteins, the newly cleaved coding region is joined to a separate coding region with added nucleotides in between, that were added by a DNA transferase. Note: Rag-1 and Rag-2 interact with both strands of DNA. A scientist would want to knockout the Rag-1 gene for viewing the effects at the molecular level as well as using these type of organisms for research on human diseases. A main reason to knockout the Rag-1 gene is to see how it will affect the entire V(D)J recombination process. By knocking the Rag-1 gene out, one will be able to see where the process is interrupted, if it is interrupted. Researchers will also be able to see if other receptors on lymphocytes, such as IL2, are affected. In V(D)J recombination, Rag-1 interacts closely with Rag-2 to instigate recombination (Godderz and Rodgers). If one were to knock out this gene, the results would show if the expression of the Rag-2 gene would be affected. Researchers could also see if both Rag proteins are crucial for recombination, or if just one is needed. Rag-1 transcripts are also found in the brain in mice (Mombaerts

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