Structural highlights
Function
[TNR16_HUMAN] Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Low affinity receptor which can bind to NGF, BDNF, NT-3, and NT-4. Can mediate cell survival as well as cell death of neural cells.[1]
Publication Abstract from PubMed
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 (p75NTR) 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 p75NTR 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 p75NTR 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.
Structural basis of death domain signaling in the p75 neurotrophin receptor.,Lin Z, Tann JY, Goh ET, Kelly C, Lim KB, Gao JF, Ibanez CF Elife. 2015 Dec 8;4. pii: e11692. doi: 10.7554/eLife.11692. PMID:26646181[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mi S, Lee X, Shao Z, Thill G, Ji B, Relton J, Levesque M, Allaire N, Perrin S, Sands B, Crowell T, Cate RL, McCoy JM, Pepinsky RB. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci. 2004 Mar;7(3):221-8. Epub 2004 Feb 15. PMID:14966521 doi:http://dx.doi.org/10.1038/nn1188
- ↑ Lin Z, Tann JY, Goh ET, Kelly C, Lim KB, Gao JF, Ibanez CF. Structural basis of death domain signaling in the p75 neurotrophin receptor. Elife. 2015 Dec 8;4. pii: e11692. doi: 10.7554/eLife.11692. PMID:26646181 doi:http://dx.doi.org/10.7554/eLife.11692
