2N97: DD homodimer

Citation:
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.
PDB ID: 2N97Download
MMDB ID: 138709
PDB Deposition Date: 2015/11/7
Updated in MMDB: 2018/05
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2N97: dimeric; determined by author
Molecular Components in 2N97
Label Count Molecule
Proteins (2 molecules)
2
Tumor Necrosis Factor Receptor Superfamily Member 16(Gene symbol: NGFR)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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