PDBsum entry 4zlp

Transcription

PDB id: 4zlp

Contents

Protein chains

241 a.a.

218 a.a.

Ligands

NAG-NAG-MAN-MAN

GOL ×3

ACT ×2

NAG

Metals

_CA ×6

Waters ×148

PDB id:

4zlp

Name:

Transcription

Title:

Crystal structure of notch3 negative regulatory region

Structure:

Neurogenic locus notch homolog protein 3. Chain: a, b. Synonym: notch 3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: notch3. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293s gnti-

Resolution:

2.48Å R-factor: 0.180 R-free: 0.204

Authors:

X.Xu,S.C.Blacklow

Key ref:

X.Xu et al. (2015). Insights into Autoregulation of Notch3 from Structural and Functional Studies of Its Negative Regulatory Region. Structure, 23, 1227-1235. PubMed id: 26051713 DOI: 10.1016/j.str.2015.05.001

Date:

01-May-15 Release date: 19-Aug-15

Protein chain

Q9UM47  (NOTC3_HUMAN) -  Neurogenic locus notch homolog protein 3 from Homo sapiens

Seq: 2321 a.a.

Struc: 241 a.a.

Protein chain

Q9UM47  (NOTC3_HUMAN) -  Neurogenic locus notch homolog protein 3 from Homo sapiens

Seq: 2321 a.a.

Struc: 218 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/j.str.2015.05.001

Structure 23:1227-1235 (2015)

PubMed id: 26051713

Insights into Autoregulation of Notch3 from Structural and Functional Studies of Its Negative Regulatory Region.

X.Xu, S.H.Choi, T.Hu, K.Tiyanont, R.Habets, A.J.Groot, M.Vooijs, J.C.Aster, R.Chopra, C.Fryer, S.C.Blacklow.

ABSTRACT

Notch receptors are transmembrane proteins that undergo activating proteolysis in response to ligand stimulation. A negative regulatory region (NRR) maintains receptor quiescence by preventing protease cleavage prior to ligand binding. We report here the X-ray structure of the NRR of autoinhibited human Notch3, and compare it with the Notch1 and Notch2 NRRs. The overall architecture of the autoinhibited conformation, in which three LIN12-Notch repeat (LNR) modules wrap around a heterodimerization domain, is preserved in Notch3, but the autoinhibited conformation of the Notch3 NRR is less stable. The Notch3 NRR uses a highly conserved surface on the third LNR module to form a dimer in the crystal. Similar homotypic interfaces exist in Notch1 and Notch2. Together, these studies reveal distinguishing structural features associated with increased basal activity of Notch3, demonstrate increased ligand-independent signaling for disease-associated mutations that map to the Notch3 NRR, and identify a conserved dimerization interface present in multiple Notch receptors.