2oo4: Difference between revisions

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==Overview==

Notch receptors transmit signals between adjacent cells. Signaling is, initiated when ligand binding induces metalloprotease cleavage of Notch, within an extracellular negative regulatory region (NRR). We present here, the X-ray structure of the human NOTCH2 NRR, which adopts an autoinhibited, conformation. Extensive interdomain interactions within the NRR bury the, metalloprotease site, showing that a substantial conformational movement, is necessary to expose this site during activation by ligand., Leukemia-associated mutations in NOTCH1 probably release autoinhibition by, destabilizing the conserved hydrophobic core of the NRR.

Notch receptors transmit signals between adjacent cells. Signaling is initiated when ligand binding induces metalloprotease cleavage of Notch within an extracellular negative regulatory region (NRR). We present here the X-ray structure of the human NOTCH2 NRR, which adopts an autoinhibited conformation. Extensive interdomain interactions within the NRR bury the metalloprotease site, showing that a substantial conformational movement is necessary to expose this site during activation by ligand. Leukemia-associated mutations in NOTCH1 probably release autoinhibition by destabilizing the conserved hydrophobic core of the NRR.

==Disease==

Known disease associated with this structure: Alagille syndrome 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600275 600275]]

==About this Structure==

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: Aster, J.C.]]

[[Category: Aster, J C.]]

[[Category: Blacklow, S.C.]]

[[Category: Blacklow, S C.]]

[[Category: Gordon, W.R.]]

[[Category: Gordon, W R.]]

[[Category: Histen, G.]]

[[Category: Sanchez-Irizarry, C.]]

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[[Category: alpha-beta-sandwich; sea domain; lnr; lin12 notch repeat; cysteine-rich; hd domain]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Jan 23 14~~:59:03 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:20:38 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-Notch receptors transmit signals between adjacent cells. Signaling is, initiated when ligand binding induces metalloprotease cleavage of Notch, within an extracellular negative regulatory region (NRR). We present here, the X-ray structure of the human NOTCH2 NRR, which adopts an autoinhibited, conformation. Extensive interdomain interactions within the NRR bury the, metalloprotease site, showing that a substantial conformational movement, is necessary to expose this site during activation by ligand., Leukemia-associated mutations in NOTCH1 probably release autoinhibition by, destabilizing the conserved hydrophobic core of the NRR.
+Notch receptors transmit signals between adjacent cells. Signaling is initiated when ligand binding induces metalloprotease cleavage of Notch within an extracellular negative regulatory region (NRR). We present here the X-ray structure of the human NOTCH2 NRR, which adopts an autoinhibited conformation. Extensive interdomain interactions within the NRR bury the metalloprotease site, showing that a substantial conformational movement is necessary to expose this site during activation by ligand. Leukemia-associated mutations in NOTCH1 probably release autoinhibition by destabilizing the conserved hydrophobic core of the NRR.
+==Disease==
+Known disease associated with this structure: Alagille syndrome 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600275 600275]]
 ==About this Structure==
@@ Line 13: / Line 16: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Aster, J.C.]]
+[[Category: Aster, J C.]]
-[[Category: Blacklow, S.C.]]
+[[Category: Blacklow, S C.]]
-[[Category: Gordon, W.R.]]
+[[Category: Gordon, W R.]]
 [[Category: Histen, G.]]
 [[Category: Sanchez-Irizarry, C.]]
@@ Line 24: / Line 27: @@
 [[Category: alpha-beta-sandwich; sea domain; lnr; lin12 notch repeat; cysteine-rich; hd domain]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:59:03 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:20:38 2008''