7ASY

Transmembrane helix of tumor necrosis factor alpha in trifluorethanol

7ASY の概要

• エントリーDOI: 10.2210/pdb7asy/pdb
• NMR情報: BMRB: 34567
• 分子名称: Tumor necrosis factor (1 entity in total)
• 機能のキーワード: transmembrane domain, helix, trifluorethanol, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3701.50

構造登録者

Guschtschin-Schmidt, N.,Muhle-Goll, C. (登録日: 2020-10-28, 公開日: 2020-12-09, 最終更新日: 2024-05-15)

主引用文献

Spitz, C.,Schlosser, C.,Guschtschin-Schmidt, N.,Stelzer, W.,Menig, S.,Gotz, A.,Haug-Kroper, M.,Scharnagl, C.,Langosch, D.,Muhle-Goll, C.,Fluhrer, R.
Non-canonical Shedding of TNF alpha by SPPL2a Is Determined by the Conformational Flexibility of Its Transmembrane Helix.
Iscience, 23:101775-101775, 2020

PubMed Abstract: Ectodomain (EC) shedding defines the proteolytic removal of a membrane protein EC and acts as an important molecular switch in signaling and other cellular processes. Using tumor necrosis factor (TNF)α as a model substrate, we identify a non-canonical shedding activity of SPPL2a, an intramembrane cleaving aspartyl protease of the GxGD type. Proline insertions in the TNFα transmembrane (TM) helix strongly increased SPPL2a non-canonical shedding, while leucine mutations decreased this cleavage. Using biophysical and structural analysis, as well as molecular dynamic simulations, we identified a flexible region in the center of the TNFα wildtype TM domain, which plays an important role in the processing of TNFα by SPPL2a. This study combines molecular biology, biochemistry, and biophysics to provide insights into the dynamic architecture of a substrate's TM helix and its impact on non-canonical shedding. Thus, these data will provide the basis to identify further physiological substrates of non-canonical shedding in the future.

PubMed: 33294784
DOI: 10.1016/j.isci.2020.101775

実験手法

SOLUTION NMR