PDBsum entry 2n83

Signaling protein/transferase

PDB id: 2n83

Contents

Protein chains

94 a.a.

105 a.a.

PDB id:

2n83

Name:

Signaling protein/transferase

Title:

P75ntr dd:rip2 card

Structure:

Tumor necrosis factor receptor superfamily member 16. Chain: a. Fragment: unp residues 334-427. Synonym: gp80-lngfr, low affinity neurotrophin receptor p75ntr, low- affinity nerve growth factor receptor, ngf receptor, p75 icd. Engineered: yes. Receptor-interacting serine/threonine-protein kinase 2. Chain: b. Fragment: unp residues 435-539.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ngfr, tnfrsf16. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ripk2, cardiak, rick, rip2, unq277/pro314/pro34092.

NMR struc:

10 models

Authors:

Z.Lin,C.F.Ibanez

Key ref:

Z.Lin et al. (2015). Structural basis of death domain signaling in the p75 neurotrophin receptor. Elife, 4, e11692. PubMed id: 26646181 DOI: 10.7554/eLife.11692

Date:

02-Oct-15 Release date: 23-Dec-15

Protein chain

P08138  (TNR16_HUMAN) -  Tumor necrosis factor receptor superfamily member 16 from Homo sapiens

Seq: 427 a.a.

Struc: 94 a.a.

Protein chain

O43353  (RIPK2_HUMAN) -  Receptor-interacting serine/threonine-protein kinase 2 from Homo sapiens

Seq: 540 a.a.

Struc: 105 a.a.

Enzyme reactions

• Enzyme class 2: Chain B: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺
• Enzyme class 3: Chain B: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.7554/eLife.11692

Elife 4:e11692 (2015)

PubMed id: 26646181

Structural basis of death domain signaling in the p75 neurotrophin receptor.

Z.Lin, J.Y.Tann, E.T.Goh, C.Kelly, K.B.Lim, J.F.Gao, C.F.Ibanez.

ABSTRACT

Death domains (DDs) mediate assembly of oligomeric complexes for activation of downstream signaling pathways through incompletely understood mechanisms. Here we report structures of complexes formed by the DD of p75 neurotrophin receptor (p75(NTR)) with RhoGDI, for activation of the RhoA pathway, with caspase recruitment domain (CARD) of RIP2 kinase, for activation of the NF-kB pathway, and with itself, revealing how DD dimerization controls access of intracellular effectors to the receptor. RIP2 CARD and RhoGDI bind to p75(NTR) DD at partially overlapping epitopes with over 100-fold difference in affinity, revealing the mechanism by which RIP2 recruitment displaces RhoGDI upon ligand binding. The p75(NTR) DD forms non-covalent, low-affinity symmetric dimers in solution. The dimer interface overlaps with RIP2 CARD but not RhoGDI binding sites, supporting a model of receptor activation triggered by separation of DDs. These structures reveal how competitive protein-protein interactions orchestrate the hierarchical activation of downstream pathways in non-catalytic receptors.