Sandbox GGC9: Difference between revisions
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==Structure of RAG1/2-DNA Strand Transfer Complex (paired conformation)== | =='''Structure of RAG1/2-DNA Strand Transfer Complex (paired conformation)'''== | ||
<StructureSection load='6XNY' size='340' side='right' caption='Structure of RAG1/2-DNA Strand Transfer Complex (Paired Conformation)' scene='75/752271/Rag_complex_background/1'> | <StructureSection load='6XNY' size='340' side='right' caption='Structure of RAG1/2-DNA Strand Transfer Complex (Paired Conformation)' scene='75/752271/Rag_complex_background/1'> | ||
RAG1 is the catalytic component of the RAG Complex. Together with RAG2, the RAG Complex functions to create antibodies for virtually any antigen. | RAG1 is the catalytic component of the RAG Complex. Together with RAG2, the RAG Complex functions to create antibodies for virtually any antigen. | ||
== Function == | == '''Function''' == | ||
RAG1 and RAG2 form the RAG Complex (RAG Recombinases), which is responsible for regulating the DNA cleavage phase during recombination. V(D)J recombination functions to produce a plethora of immune molecules in developing B and T-lymphocytes. The V stands for variable, D, diversity and J joining of the gene segments. RAG1 functions as the catalytic portion while RAG2, although not catalytic, is required for RAG1 to function.[1] RAG1 controls the ability of the DNA to bind to the RSS or recombination signal sequences. This is achieved by the ability of the RAG1 complex to create a double-stranded break between the (RSS) and the adjacent coding sequence. This process is executed in the following way: introduction of a nick, creating a 3'-hydroxyl group which attacks the phosphodiester bond on the opposite strand.[1] This is a direct transesterification reaction which results in four DNA ends. Histones also assist in the nicking and hairpinning of the strands. The result is the recombination of variable genes joining.[1] Additionally to the role played in V(D)J, RAG also assists in pre-B cell allelic exclusion. This means that there is a recombination of the second allele. RAG1 also possess ubiquitin properties. Newer Studies suggest that the RAG1/2 recombinase complex acts as a domesticated transposase.[2] | RAG1 and RAG2 form the RAG Complex (RAG Recombinases), which is responsible for regulating the DNA cleavage phase during recombination. V(D)J recombination functions to produce a plethora of immune molecules in developing B and T-lymphocytes. The V stands for variable, D, diversity and J joining of the gene segments. RAG1 functions as the catalytic portion while RAG2, although not catalytic, is required for RAG1 to function.[1] RAG1 controls the ability of the DNA to bind to the RSS or recombination signal sequences. This is achieved by the ability of the RAG1 complex to create a double-stranded break between the (RSS) and the adjacent coding sequence. This process is executed in the following way: introduction of a nick, creating a 3'-hydroxyl group which attacks the phosphodiester bond on the opposite strand.[1] This is a direct transesterification reaction which results in four DNA ends. Histones also assist in the nicking and hairpinning of the strands. The result is the recombination of variable genes joining.[1] Additionally to the role played in V(D)J, RAG also assists in pre-B cell allelic exclusion. This means that there is a recombination of the second allele. RAG1 also possess ubiquitin properties. Newer Studies suggest that the RAG1/2 recombinase complex acts as a domesticated transposase.[2] | ||
== Disease == | == '''Disease''' == | ||
Mutations of the RAG recombinases are often occurring in patients being displaying immunodeficiency and Omenn syndrome. [3] Omenn's syndrome is a severe combined immunodeficiency. [4] Some characteristics include redness of skin, peeling skin, hair loss, chronic diarrhea, enlarged lymph nodes, swelling of liver and spleen, and increased levels of of serum IgE. [4] | Mutations of the RAG recombinases are often occurring in patients being displaying immunodeficiency and Omenn syndrome. [3] Omenn's syndrome is a severe combined immunodeficiency. [4] Some characteristics include redness of skin, peeling skin, hair loss, chronic diarrhea, enlarged lymph nodes, swelling of liver and spleen, and increased levels of of serum IgE. [4] | ||
== Relevance == | == '''Relevance''' == | ||
Early intervention of people with Omenn's syndrome is important, because if left untreated it will be fatal. [4] Treatment of Omenn's syndrome includes bone marrow or cord blood stem cell transplantation. [4] | Early intervention of people with Omenn's syndrome is important, because if left untreated it will be fatal. [4] Treatment of Omenn's syndrome includes bone marrow or cord blood stem cell transplantation. [4] | ||
== Structural highlights == | == '''Structural highlights''' == | ||
The subunit structure is defined as a homodimer. | The subunit structure is defined as a homodimer. | ||
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</StructureSection> | </StructureSection> | ||
== References == | == '''References''' == | ||
<references/> | <references/> | ||