{PDOC51487}
{PS51487; NBD}
{BEGIN}
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* NBD domain profile *
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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 [1].

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 [2]. 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 [3].

The profile we developed covers the entire NBD domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: April 2010 / First entry.

[ 1] Difilippantonio M.J., McMahan C.J., Eastman Q.M., Spanopoulou E.,
     Schatz D.G.
     "RAG1 mediates signal sequence recognition and recruitment of RAG2 in
     V(D)J recombination."
     Cell 87:253-262(1996).
     PubMed=8861909
[ 2] Spanopoulou E., Zaitseva F., Wang F.-H., Santagata S., Baltimore D.,
     Panayotou G.
     "The homeodomain region of Rag-1 reveals the parallel mechanisms of
     bacterial and V(D)J recombination."
     Cell 87:263-276(1996).
     PubMed=8861910
[ 3] Yin F.F., Bailey S., Innis C.A., Ciubotaru M., Kamtekar S.,
     Steitz T.A., Schatz D.G.
     "Structure of the RAG1 nonamer binding domain with DNA reveals a dimer
     that mediates DNA synapsis."
     Nat. Struct. Mol. Biol. 16:499-508(2009).
     PubMed=19396172; DOI=10.1038/nsmb.1593

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