Self-association of a highly charged arginine-rich cell-penetrating peptide
Tesei, Giulio LU ; Vazdar, Mario ; Jensen, Malene Ringkjøbing ; Cragnell, Carolina LU ; Mason, Phil E ; Heyda, Jan ; Skepö, Marie LU ; Jungwirth, Pavel and Lund, Mikael LU
(2017)
In Proceedings of the National Academy of Sciences of the United States of America
114(43).
p.11428-11433
- Abstract
Small-angle X-ray scattering (SAXS) measurements reveal a striking difference in intermolecular interactions between two short highly charged peptides - deca-arginine (R10) and deca-lysine (K10). Comparison of SAXS curves at high and low salt concentration shows that R10 self-associates, while interactions between K10 chains are purely repulsive. The self-association of R10 is stronger at lower ionic strengths, indicating that the attraction between R10 molecules has an important electrostatic component. SAXS data are complemented by NMR measurements and potentials of mean force between the peptides, calculated by means of umbrella-sampling molecular dynamics (MD) simulations. All-atom MD simulations elucidate the origin of the R10- R10... (More)
Small-angle X-ray scattering (SAXS) measurements reveal a striking difference in intermolecular interactions between two short highly charged peptides - deca-arginine (R10) and deca-lysine (K10). Comparison of SAXS curves at high and low salt concentration shows that R10 self-associates, while interactions between K10 chains are purely repulsive. The self-association of R10 is stronger at lower ionic strengths, indicating that the attraction between R10 molecules has an important electrostatic component. SAXS data are complemented by NMR measurements and potentials of mean force between the peptides, calculated by means of umbrella-sampling molecular dynamics (MD) simulations. All-atom MD simulations elucidate the origin of the R10- R10 attraction by providing structural information on the dimeric state. The last two C-terminal residues of R10 constitute an adhesive patch formed by stacking of the side chains of two arginine residues and by salt bridges formed between the like-charge ion pair and the C-terminal carboxyl groups. A statistical analysis of the Protein Data Bank reveals that this mode of interaction is a common feature in proteins.
(Less)
- author
- Tesei, Giulio
LU
; Vazdar, Mario
; Jensen, Malene Ringkjøbing
; Cragnell, Carolina
LU
; Mason, Phil E
; Heyda, Jan
; Skepö, Marie
LU
; Jungwirth, Pavel
and Lund, Mikael
LU
- organization
- publishing date
- 2017-10-24
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Cell-penetrating peptide, MD simulations, NMR, SAXS, Self-association
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 114
- issue
- 43
- pages
- 6 pages
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000413520700061
- pmid:29073067
- scopus:85032021633
- ISSN
- 0027-8424
- DOI
- 10.1073/pnas.1712078114
- language
- English
- LU publication?
- yes
- id
- d17966db-786f-4d12-a5f5-3a25a837ce80
- date added to LUP
- 2017-11-02 12:32:30
- date last changed
- 2024-07-08 04:04:15
@article{d17966db-786f-4d12-a5f5-3a25a837ce80,
abstract = {{<p>Small-angle X-ray scattering (SAXS) measurements reveal a striking difference in intermolecular interactions between two short highly charged peptides - deca-arginine (R10) and deca-lysine (K10). Comparison of SAXS curves at high and low salt concentration shows that R10 self-associates, while interactions between K10 chains are purely repulsive. The self-association of R10 is stronger at lower ionic strengths, indicating that the attraction between R10 molecules has an important electrostatic component. SAXS data are complemented by NMR measurements and potentials of mean force between the peptides, calculated by means of umbrella-sampling molecular dynamics (MD) simulations. All-atom MD simulations elucidate the origin of the R10- R10 attraction by providing structural information on the dimeric state. The last two C-terminal residues of R10 constitute an adhesive patch formed by stacking of the side chains of two arginine residues and by salt bridges formed between the like-charge ion pair and the C-terminal carboxyl groups. A statistical analysis of the Protein Data Bank reveals that this mode of interaction is a common feature in proteins.</p>}},
author = {{Tesei, Giulio and Vazdar, Mario and Jensen, Malene Ringkjøbing and Cragnell, Carolina and Mason, Phil E and Heyda, Jan and Skepö, Marie and Jungwirth, Pavel and Lund, Mikael}},
issn = {{0027-8424}},
keywords = {{Cell-penetrating peptide; MD simulations; NMR; SAXS; Self-association}},
language = {{eng}},
month = {{10}},
number = {{43}},
pages = {{11428--11433}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences of the United States of America}},
title = {{Self-association of a highly charged arginine-rich cell-penetrating peptide}},
url = {{http://dx.doi.org/10.1073/pnas.1712078114}},
doi = {{10.1073/pnas.1712078114}},
volume = {{114}},
year = {{2017}},
}