8FNB

Crystal structure of the C-terminal Fg domain of human TNC with the mutations Y2140H and S2164H

8FNB の概要

• エントリーDOI: 10.2210/pdb8fnb/pdb
• 分子名称: Tenascin, CALCIUM ION, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: extracellular matrix, fibrinogen, signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53098.99

構造登録者

Bouyain, S. (登録日: 2022-12-27, 公開日: 2023-07-12, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.8 Å)