AI Article Synopsis
- PGRN was found to directly bind to TNF receptors (TNFR) in immune cells (specifically splenocytes), inhibiting the interaction of TNFα with these cells.
- The proper folding of PGRN is crucial for its binding to TNFR, as treatments like DTT can disrupt this interaction, while enhancing binding to another protein called Sortilin.
- Key regions (CRD2 and CRD3) of the TNFR extracellular domain are essential for the interaction with PGRN, highlighting its role in influencing anti-inflammatory responses in autoimmune diseases.
Article Abstract
We previously reported that PGRN directly bound to TNF receptors (TNFR) in vitro and in chondrocytes (Tang, et al., Science, 2011). Here we report that PGRN also associated with TNFR in splenocytes, and inhibited the binding of TNFα to immune cells. Proper folding of PGRN is essential for its binding to TNFR, as DTT treatment abolished its binding to TNFR. In contrast, the binding of PGRN to Sortilin was enhanced by DTT. Protein interaction assays with mutants of the TNFR extracellular domain demonstrated that CRD2 and CRD3 of TNFR are important for the interaction with PGRN, similar to the binding to TNFα. Taken together, these findings provide the molecular basis underlying PGRN/TNFR interaction and PGRN-mediated anti-inflammatory activity in various autoimmune diseases and conditions.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826980 | PMC |
| http://dx.doi.org/10.1016/j.febslet.2013.09.024 | DOI Listing |
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