6KLM
NMR solution structure of Roseltide rT7
Summary for 6KLM
| Entry DOI | 10.2210/pdb6klm/pdb |
| NMR Information | BMRB: 36273 |
| Descriptor | Roseltide rT7 (1 entity in total) |
| Functional Keywords | roseltide, plant protein |
| Biological source | Hibiscus sabdariffa |
| Total number of polymer chains | 1 |
| Total formula weight | 3707.39 |
| Authors | |
| Primary citation | 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 Cited by 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: 31727740DOI: 10.1074/jbc.RA119.010796 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
