7L54

Solution NMR structure of the cyclic plant protein PDP-23 in SDS micelles

Summary for 7L54

• Entry DOI: 10.2210/pdb7l54/pdb
• Related: 7L51 7L53 7L55
• NMR Information: BMRB: 30829
• Descriptor: Cyclic plant protein PDP-23 (1 entity in total)
• Functional Keywords: macrocyclic peptide, paws derived peptide, plant protein
• Biological source: Zinnia elegans
• Total number of polymer chains: 1
• Total formula weight: 3135.51

Authors

Rosengren, K.J.,Payne, C.D. (deposition date: 2020-12-21, release date: 2021-01-20, Last modification date: 2024-11-06)

Primary citation

Payne, C.D.,Franke, B.,Fisher, M.F.,Hajiaghaalipour, F.,McAleese, C.E.,Song, A.,Eliasson, C.,Zhang, J.,Jayasena, A.S.,Vadlamani, G.,Clark, R.J.,Minchin, R.F.,Mylne, J.S.,Rosengren, K.J.
A chameleonic macrocyclic peptide with drug delivery applications.
Chem Sci, 12:6670-6683, 2021

PubMed Abstract: Head-to-tail cyclized peptides are intriguing natural products with unusual properties. The PawS-Derived Peptides (PDPs) are ribosomally synthesized as part of precursors for seed storage albumins in species of the daisy family, and are post-translationally excised and cyclized during proteolytic processing. Here we report a PDP twice the typical size and with two disulfide bonds, identified from seeds of . In water, synthetic PDP-23 forms a unique dimeric structure in which two monomers containing two β-hairpins cross-clasp and enclose a hydrophobic core, creating a square prism. This dimer can be split by addition of micelles or organic solvent and in monomeric form PDP-23 adopts open or closed V-shapes, exposing different levels of hydrophobicity dependent on conditions. This chameleonic character is unusual for disulfide-rich peptides and engenders PDP-23 with potential for cell delivery and accessing novel targets. We demonstrate this by conjugating a rhodamine dye to PDP-23, creating a stable, cell-penetrating inhibitor of the P-glycoprotein drug efflux pump.

PubMed: 34040741
DOI: 10.1039/d1sc00692d

Experimental method

SOLUTION NMR