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Notch proteins are transmembrane receptors which can transduce signals between cells.Upon binding to their ligands on the neighboring cells,notch receptors can be activated and undergo conformational changes which enable their proteolysis by ADAM-family of metalloproteases~([1]).The cleavage site of notch protein located on its hetrodimerizaton domain(HD)of the negative regulatory region(NRR)proximal to the N-terminal of the transmembrane helix.Recent crystal structures on several notch proteins~([2-4])indicated that a series of three Lin12/Notch repeats(LNRs)wrap around the HD and bury the cleavage site to prevent it from proteolysis at the normal conditions without ligand binding.Studies indicated that notch/ligand binding may al-
Notch proteins are transmembrane receptors which can transduce signals between cells. Invited binding to their ligands on the neighboring cells, notch receptors can be activated and undergo conformational changes which enable their proteolysis by ADAM-family of metalloproteases ~ ([1]). The cleavage site of notch protein located on its hetrodimerizaton domain (HD) of the negative regulatory region (NRR) proximal to the N-terminal of the transmembrane helix. Recent crystal structures on several notch proteins ~ ([2-4]) indicates that a series of three Lin12 / Notch repeats (LNRs) wrap around the HD and bury the cleavage site to prevent it from proteolysis at the normal conditions without ligand binding. Stuids indicated that notch / ligand binding may al-