1pb5
From Proteopedia
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|PDB= 1pb5 |SIZE=350|CAPTION= <scene name='initialview01'>1pb5</scene> | |PDB= 1pb5 |SIZE=350|CAPTION= <scene name='initialview01'>1pb5</scene> | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM ION'>CA</scene> | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pb5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pb5 OCA], [http://www.ebi.ac.uk/pdbsum/1pb5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pb5 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Notch1 is a member of a conserved family of large modular heterodimeric type 1 transmembrane receptors that control differentiation in multicellular animals. Receptor maturation is accompanied by a furin-dependent cleavage that converts the Notch1 precursor polypeptide into a heterodimer consisting of an extracellular ligand-binding subunit (NEC) and a transmembrane signaling subunit (NTM). Binding of a physiologic ligand to NEC induces signaling by triggering additional proteolytic cleavages in NTM, which allow its intracellular region to translocate to the nucleus where it participates in a transcriptional activation complex. In the absence of ligand, the three conserved LNR modules of the NEC subunit participate in maintaining the receptor in its resting conformation. Here, we report the solution structure of the first LNR module (LNR_A) of human Notch1, and identify residues of LNR_A perturbed by the presence of the adjacent module LNR_B. LNR_A is held together by a unique arrangement of three disulfide bonds and a single bound Ca(2+) ion, and adopts a novel fold that falls in the general class of irregular disulfide-bonded structures. Residues perturbed by the presence of the adjacent LNR_B module are predominantly hydrophobic, and lie on one face of the module. These studies represent an initial step toward understanding the structural interrelationships among the three contiguous LNR modules required for proper regulation of Notch signaling. | Notch1 is a member of a conserved family of large modular heterodimeric type 1 transmembrane receptors that control differentiation in multicellular animals. Receptor maturation is accompanied by a furin-dependent cleavage that converts the Notch1 precursor polypeptide into a heterodimer consisting of an extracellular ligand-binding subunit (NEC) and a transmembrane signaling subunit (NTM). Binding of a physiologic ligand to NEC induces signaling by triggering additional proteolytic cleavages in NTM, which allow its intracellular region to translocate to the nucleus where it participates in a transcriptional activation complex. In the absence of ligand, the three conserved LNR modules of the NEC subunit participate in maintaining the receptor in its resting conformation. Here, we report the solution structure of the first LNR module (LNR_A) of human Notch1, and identify residues of LNR_A perturbed by the presence of the adjacent module LNR_B. LNR_A is held together by a unique arrangement of three disulfide bonds and a single bound Ca(2+) ion, and adopts a novel fold that falls in the general class of irregular disulfide-bonded structures. Residues perturbed by the presence of the adjacent LNR_B module are predominantly hydrophobic, and lie on one face of the module. These studies represent an initial step toward understanding the structural interrelationships among the three contiguous LNR modules required for proper regulation of Notch signaling. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Aortic valve disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190198 190198]], Leukemia, T-cell acute lymphoblastic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190198 190198]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Sanchez-Irizarry, C.]] | [[Category: Sanchez-Irizarry, C.]] | ||
[[Category: Vardar, D.]] | [[Category: Vardar, D.]] | ||
| - | [[Category: CA]] | ||
[[Category: calcium-binding domain]] | [[Category: calcium-binding domain]] | ||
[[Category: disulfide bond]] | [[Category: disulfide bond]] | ||
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[[Category: protein module]] | [[Category: protein module]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:57:20 2008'' |
Revision as of 19:57, 30 March 2008
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| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
NMR Structure of a Prototype LNR Module from Human Notch1
Overview
Notch1 is a member of a conserved family of large modular heterodimeric type 1 transmembrane receptors that control differentiation in multicellular animals. Receptor maturation is accompanied by a furin-dependent cleavage that converts the Notch1 precursor polypeptide into a heterodimer consisting of an extracellular ligand-binding subunit (NEC) and a transmembrane signaling subunit (NTM). Binding of a physiologic ligand to NEC induces signaling by triggering additional proteolytic cleavages in NTM, which allow its intracellular region to translocate to the nucleus where it participates in a transcriptional activation complex. In the absence of ligand, the three conserved LNR modules of the NEC subunit participate in maintaining the receptor in its resting conformation. Here, we report the solution structure of the first LNR module (LNR_A) of human Notch1, and identify residues of LNR_A perturbed by the presence of the adjacent module LNR_B. LNR_A is held together by a unique arrangement of three disulfide bonds and a single bound Ca(2+) ion, and adopts a novel fold that falls in the general class of irregular disulfide-bonded structures. Residues perturbed by the presence of the adjacent LNR_B module are predominantly hydrophobic, and lie on one face of the module. These studies represent an initial step toward understanding the structural interrelationships among the three contiguous LNR modules required for proper regulation of Notch signaling.
About this Structure
1PB5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Nuclear magnetic resonance structure of a prototype Lin12-Notch repeat module from human Notch1., Vardar D, North CL, Sanchez-Irizarry C, Aster JC, Blacklow SC, Biochemistry. 2003 Jun 17;42(23):7061-7. PMID:12795601
Page seeded by OCA on Sun Mar 30 22:57:20 2008
