6KLM

NMR solution structure of Roseltide rT7

6KLM の概要

• エントリーDOI: 10.2210/pdb6klm/pdb
• NMR情報: BMRB: 36273
• 分子名称: Roseltide rT7 (1 entity in total)
• 機能のキーワード: roseltide, plant protein
• 由来する生物種: Hibiscus sabdariffa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3707.39

構造登録者

Fan, J.S.,Kam, A.,Loo, S.,Yang, D.,Tam, P.J. (登録日: 2019-07-30, 公開日: 2019-11-20, 最終更新日: 2024-10-30)

主引用文献

Kam, A.,Loo, S.,Fan, J.S.,Sze, S.K.,Yang, D.,Tam, J.P.
Roseltide rT7 is a disulfide-rich, anionic, and cell-penetrating peptide that inhibits proteasomal degradation.
J.Biol.Chem., 294:19604-19615, 2019

PubMed Abstract: Disulfide-rich plant peptides with molecular masses of 2-6 kDa represent an expanding class of peptidyl-type natural products with diverse functions. They are structurally compact, hyperstable, and underexplored as cell-penetrating agents that inhibit intracellular functions. Here, we report the discovery of an anionic, 34-residue peptide, the disulfide-rich roseltide rT7 from (of the Malvaceae family) that penetrates cells and inhibits their proteasomal activities. Combined proteomics and NMR spectroscopy revealed that roseltide rT7 is a cystine-knotted, six-cysteine hevein-like cysteine-rich peptide. A pair-wise comparison indicated that roseltide rT7 is >100-fold more stable against protease degradation than its -alkylated analog. Confocal microscopy studies and cell-based assays disclosed that after roseltide rT7 penetrates cells, it causes accumulation of ubiquitinated proteins, inhibits human 20S proteasomes, reduces tumor necrosis factor-induced IκBα degradation, and decreases expression levels of intercellular adhesion molecule-1. Structure-activity studies revealed that roseltide rT7 uses a canonical substrate-binding mechanism for proteasomal inhibition enabled by an IIML motif embedded in its proline-rich and exceptionally long intercysteine loop 4. Taken together, our results provide mechanistic insights into a novel disulfide-rich, anionic, and cell-penetrating peptide, representing a potential lead for further development as a proteasomal inhibitor in anti-cancer or anti-inflammatory therapies.

PubMed: 31727740
DOI: 10.1074/jbc.RA119.010796

実験手法

SOLUTION NMR