8X8T

NMR structure of p75NTR juxtamembrane domain in complex with RhoGDI N-terminal domain containing a phosphorylation-mimicking S34D mutation


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

RhoGDI phosphorylation by PKC promotes its interaction with death receptor p75 NTR to gate axon growth and neuron survival.

Ramanujan, A.Li, Z.Ma, Y.Lin, Z.Ibanez, C.F.

(2024) EMBO Rep 25: 1490-1512

  • DOI: https://doi.org/10.1038/s44319-024-00064-2
  • Primary Citation of Related Structures:  
    8X8T

  • PubMed Abstract: 

    How receptors juggle their interactions with multiple downstream effectors remains poorly understood. Here we show that the outcome of death receptor p75 NTR signaling is determined through competition of effectors for interaction with its intracellular domain, in turn dictated by the nature of the ligand. While NGF induces release of RhoGDI through recruitment of RIP2, thus decreasing RhoA activity in favor of NFkB signaling, MAG induces PKC-mediated phosphorylation of the RhoGDI N-terminus, promoting its interaction with the juxtamembrane domain of p75 NTR , disengaging RIP2, and enhancing RhoA activity in detriment of NF-kB. This results in stunted neurite outgrowth and apoptosis in cerebellar granule neurons. If presented simultaneously, MAG prevails over NGF. The NMR solution structure of the complex between the RhoGDI N-terminus and p75 NTR juxtamembrane domain reveals previously unknown structures of these proteins and clarifies the mechanism of p75 NTR activation. These results show how ligand-directed competition between RIP2 and RhoGDI for p75 NTR engagement determine axon growth and neuron survival. Similar principles are likely at work in other receptors engaging multiple effectors and signaling pathways.


  • Organizational Affiliation

    Department of Physiology and Life Sciences Institute, National University of Singapore, 117456, Singapore, Singapore.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Rho GDP-dissociation inhibitor 161Homo sapiensMutation(s): 1 
Gene Names: ARHGDIA
UniProt & NIH Common Fund Data Resources
Find proteins for P52565 (Homo sapiens)
Explore P52565 
Go to UniProtKB:  P52565
PHAROS:  P52565
GTEx:  ENSG00000141522 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP52565
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Tumor necrosis factor receptor superfamily member 1662Homo sapiensMutation(s): 0 
Gene Names: NGFR
UniProt & NIH Common Fund Data Resources
Find proteins for P08138 (Homo sapiens)
Explore P08138 
Go to UniProtKB:  P08138
PHAROS:  P08138
GTEx:  ENSG00000064300 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08138
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data

  • Released Date: 2024-04-03 
  • Deposition Author(s): Lin, Z., Li, Z.

Funding OrganizationLocationGrant Number
National Natural Science Foundation of China (NSFC)China--

Revision History  (Full details and data files)

  • Version 1.0: 2024-04-03
    Type: Initial release
  • Version 1.1: 2024-05-15
    Changes: Database references