|PROSITE documentation PDOC51487|
The variable portions of immunoglobulin and T cell receptor genes are assembled in developing lymphocytes from variable (V), joining (J), and in some cases diversity (D) gene segments, which are widely separated in the genome. These segments are brought together in a highly regulated manner by a somatic site-specific recombination reaction known as V(D)J recombination. Each gene segment is flanked by a signal sequence consisting of a conserved heptamer (consensus sequence 5'-CACAGTG-3') and nonamer (consensus sequence 5'-ACAAAAACC-3') separated by a relatively nonconserved 12 or 23 base pair (bp) spacer (12 signal or 23 signal, respectively). A segment flanked by a 12 signal can only be joined efficiently to one flanked by a 23 signal, a restriction referred to as the 12/23 rule .
The V(D)J recombinase subunits Rag-1 and Rag-2 mediate assembly of antigen receptor gene segments. The critical step for signal recognition is binding of Rag-1 to the nonamer . The Rag-1 nonamer binding domain (NBD) forms a tightly interwoven dimer that binds and synapses two nonamer elements, with each NBD making contact with both DNA molecules. Each NBD monomer is composed of three helices: H1, H2 and H3 (see <PDB:3GNA>). Helix 1 contains a kink that separates it into two smaller helices: H1a and H1b. Helices H2 and H3 from each subunit form a four-helix bundle through extensive hydrophobic interactions and constitute the bulk of the dimer interface, whereas the H1 helices from the two subunits wrap around one side of the four-helix bundle with the N-terminal GGRPR motifs protruding from opposite sides of the dimer. The GGRPR motif is an example of an AT-hook, a structural element found in various DNA binding proteins .
The profile we developed covers the entire NBD domain.Last update:
April 2010 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Difilippantonio M.J. McMahan C.J. Eastman Q.M. Spanopoulou E. Schatz D.G.|
|Title||RAG1 mediates signal sequence recognition and recruitment of RAG2 in V(D)J recombination.|
|2||Authors||Spanopoulou E. Zaitseva F. Wang F.-H. Santagata S. Baltimore D. Panayotou G.|
|Title||The homeodomain region of Rag-1 reveals the parallel mechanisms of bacterial and V(D)J recombination.|
|3||Authors||Yin F.F. Bailey S. Innis C.A. Ciubotaru M. Kamtekar S. Steitz T.A. Schatz D.G.|
|Title||Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis.|
|Source||Nat. Struct. Mol. Biol. 16:499-508(2009).|