8FN9

Crystal structure of the C-terminal Fg domain of TNR with the single FN domain of PTPRZ

Summary for 8FN9

• Entry DOI: 10.2210/pdb8fn9/pdb
• Descriptor: Tenascin-R, Receptor-type tyrosine-protein phosphatase zeta, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: complex, receptor protein tyrosine phosphatase, extracellular matrix, fibronectin type iii, fibrinogen, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 156726.23

Authors

Bouyain, S. (deposition date: 2022-12-27, release date: 2023-07-12, Last modification date: 2024-11-13)

Primary citation

Sinha, A.,Kawakami, J.,Cole, K.S.,Ladutska, A.,Nguyen, M.Y.,Zalmai, M.S.,Holder, B.L.,Broerman, V.M.,Matthews, R.T.,Bouyain, S.
Protein-protein interactions between tenascin-R and RPTP zeta /phosphacan are critical to maintain the architecture of perineuronal nets.
J.Biol.Chem., 299:104952-104952, 2023

PubMed Abstract: Neural plasticity, the ability to alter the structure and function of neural circuits, varies throughout the age of an individual. The end of the hyperplastic period in the central nervous system coincides with the appearance of honeycomb-like structures called perineuronal nets (PNNs) that surround a subset of neurons. PNNs are a condensed form of neural extracellular matrix that include the glycosaminoglycan hyaluronan and extracellular matrix proteins such as aggrecan and tenascin-R (TNR). PNNs are key regulators of developmental neural plasticity and cognitive functions, yet our current understanding of the molecular interactions that help assemble them remains limited. Disruption of Ptprz1, the gene encoding the receptor protein tyrosine phosphatase RPTPζ, altered the appearance of nets from a reticulated structure to puncta on the surface of cortical neuron bodies in adult mice. The structural alterations mirror those found in Tnr mice, and TNR is absent from the net structures that form in dissociated cultures of Ptprz1 cortical neurons. These findings raised the possibility that TNR and RPTPζ cooperate to promote the assembly of PNNs. Here, we show that TNR associates with the RPTPζ ectodomain and provide a structural basis for these interactions. Furthermore, we show that RPTPζ forms an identical complex with tenascin-C, a homolog of TNR that also regulates neural plasticity. Finally, we demonstrate that mutating residues at the RPTPζ-TNR interface impairs the formation of PNNs in dissociated neuronal cultures. Overall, this work sets the stage for analyzing the roles of protein-protein interactions that underpin the formation of nets.

PubMed: 37356715
DOI: 10.1016/j.jbc.2023.104952

Experimental method

X-RAY DIFFRACTION (1.8 Å)