Ghent University Academic Bibliography

Advanced

The solution structure and self-association properties of the cyclic lipodepsipeptide pseudodesmin A support its pore-forming potential

Davy Sinnaeve UGent, Pieter Hendrickx UGent, Johan Van Hemel, Eric Peys, Bruno Kieffer and José Martins UGent (2009) CHEMISTRY-A EUROPEAN JOURNAL. 15(46). p.12653-12662
abstract
Pseudodesmin A is a cyclic lipodepsipeptide (CLP) of the viscosin group with a moderate in vitro biological activity. For several CLPs, including members of this group, this activity has been related to the ability to form ion pores in cellular membranes. As their size does not allow individual CLPs to span the membrane bilayer, individual monomers must somehow assemble into a larger structure. NMR spectroscopy has been used to demonstrate that in chloroform and other apolar organic solvents, pseudodesmin A monomers assemble into a supramolecular structure. These self-assembled structures can become sufficiently large to span the membrane bilayer as demonstrated with translational diffusion NMR spectroscopic measurements. With the aim to obtain more insight into the structural nature of this assembly, the solution conformation of pseudodesmin A was first determined by using ROESY (rOe) restraints measured in acetonitrile, in which no selfassociation occurs. The structure, which is found to be mostly similar to the previously described crystal structure, is shown to be retained within the supramolecular complex. Intermolecular rOe contacts obtained in chloroform together with chemical shift perturbation data provides structural insight into the organization of the selfassociated complex. Based upon this analysis, a model for the organization of pseudodesmin A monomers in the supramolecular assembly is proposed, which is in agreement with the formation of bilayer spanning hydrophilic pores and provides the basis for a structure–function relationship for this type of CLPs. Finally, it is demonstrated that the differences previously reported between the crystal and solution conformation of the white line inducing principle (WLIP), a close analogue of pseudodesmin A, are the result of the use of dimethyl sulfoxide as solvent, whose strong hydrogen-bonding capacity induces conformational exchange.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
NMR spectroscopy, cyclic lipodepsipeptide, ion channels, self-assembly, peptides, PSEUDOMONAS-REACTANS, ANTIMICROBIAL PEPTIDES, NMR-SPECTROSCOPY, COUPLING-CONSTANTS, PSEUDOPHOMIN-B, MODEL, FLUORESCENS, CHEMISTRY, WLIP
journal title
CHEMISTRY-A EUROPEAN JOURNAL
Chem.-Eur. J.
volume
15
issue
46
pages
12653 - 12662
Web of Science type
Article
Web of Science id
000272509500017
JCR category
CHEMISTRY, MULTIDISCIPLINARY
JCR impact factor
5.382 (2009)
JCR rank
16/137 (2009)
JCR quartile
1 (2009)
ISSN
0947-6539
DOI
10.1002/chem.200901885
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
784824
handle
http://hdl.handle.net/1854/LU-784824
date created
2009-11-19 11:56:12
date last changed
2010-06-15 15:13:08
@article{784824,
  abstract     = {Pseudodesmin A is a cyclic lipodepsipeptide (CLP) of the viscosin group with a moderate in vitro biological activity. For several CLPs, including members of this group, this activity has been related to the ability to form ion pores in cellular membranes. As their size does not allow individual CLPs to span the membrane bilayer, individual monomers must somehow assemble into a larger structure. NMR spectroscopy has been used to demonstrate that in chloroform and other apolar organic solvents, pseudodesmin A monomers assemble into a supramolecular structure. These self-assembled structures can become sufficiently large to span the membrane bilayer as demonstrated with translational diffusion NMR spectroscopic measurements. With the aim to obtain more insight into the structural nature of this assembly, the solution conformation of pseudodesmin A was first determined by using ROESY (rOe) restraints measured in acetonitrile, in which no selfassociation occurs. The structure, which is found to be mostly similar to the previously described crystal structure, is shown to be retained within the supramolecular complex. Intermolecular rOe contacts obtained in chloroform together with chemical shift perturbation data provides structural insight into the organization of the selfassociated complex. Based upon this analysis, a model for the organization of pseudodesmin A monomers in the supramolecular assembly is proposed, which is in agreement with the formation of bilayer spanning hydrophilic pores and provides the basis for a structure--function relationship for this type of CLPs. Finally, it is demonstrated that the differences previously reported between the crystal and solution conformation of the white line inducing principle (WLIP), a close analogue of pseudodesmin A, are the result of the use of dimethyl sulfoxide as solvent, whose strong hydrogen-bonding capacity induces conformational exchange.},
  author       = {Sinnaeve, Davy and Hendrickx, Pieter and Van Hemel, Johan and Peys, Eric and Kieffer, Bruno and Martins, Jos{\'e}},
  issn         = {0947-6539},
  journal      = {CHEMISTRY-A EUROPEAN JOURNAL},
  keyword      = {NMR spectroscopy,cyclic lipodepsipeptide,ion channels,self-assembly,peptides,PSEUDOMONAS-REACTANS,ANTIMICROBIAL PEPTIDES,NMR-SPECTROSCOPY,COUPLING-CONSTANTS,PSEUDOPHOMIN-B,MODEL,FLUORESCENS,CHEMISTRY,WLIP},
  language     = {eng},
  number       = {46},
  pages        = {12653--12662},
  title        = {The solution structure and self-association properties of the cyclic lipodepsipeptide pseudodesmin A support its pore-forming potential},
  url          = {http://dx.doi.org/10.1002/chem.200901885},
  volume       = {15},
  year         = {2009},
}

Chicago
Sinnaeve, Davy, Pieter Hendrickx, Johan Van Hemel, Eric Peys, Bruno Kieffer, and José Martins. 2009. “The Solution Structure and Self-association Properties of the Cyclic Lipodepsipeptide Pseudodesmin A Support Its Pore-forming Potential.” Chemistry-a European Journal 15 (46): 12653–12662.
APA
Sinnaeve, D., Hendrickx, P., Van Hemel, J., Peys, E., Kieffer, B., & Martins, J. (2009). The solution structure and self-association properties of the cyclic lipodepsipeptide pseudodesmin A support its pore-forming potential. CHEMISTRY-A EUROPEAN JOURNAL, 15(46), 12653–12662.
Vancouver
1.
Sinnaeve D, Hendrickx P, Van Hemel J, Peys E, Kieffer B, Martins J. The solution structure and self-association properties of the cyclic lipodepsipeptide pseudodesmin A support its pore-forming potential. CHEMISTRY-A EUROPEAN JOURNAL. 2009;15(46):12653–62.
MLA
Sinnaeve, Davy, Pieter Hendrickx, Johan Van Hemel, et al. “The Solution Structure and Self-association Properties of the Cyclic Lipodepsipeptide Pseudodesmin A Support Its Pore-forming Potential.” CHEMISTRY-A EUROPEAN JOURNAL 15.46 (2009): 12653–12662. Print.