Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

A de Novo Designed Coiled-Coil Peptide with a Reversible pH-Induced Oligomerization Switch

LIZATOVIC, ROBERT LU ; Aurelius, Oskar LU ; Stenström, Olof LU ; Drakenberg, Torbjörn LU ; Akke, Mikael LU orcid ; Logan, Derek T. LU orcid and André, Ingemar LU orcid (2016) In Structure 24(6). p.946-955
Abstract

Protein conformational switches have many useful applications but are difficult to design rationally. Here we demonstrate how the isoenergetic energy landscape of higher-order coiled coils can enable the formation of an oligomerization switch by insertion of a single destabilizing element into an otherwise stable computationally designed scaffold. We describe a de novo designed peptide that was discovered to switch between a parallel symmetric pentamer at pH 8 and a trimer of antiparallel dimers at pH 6. The transition between pentamer and hexamer is caused by changes in the protonation states of glutamatic acid residues with highly upshifted pKa values in both oligomer forms. The drastic conformational change coupled with... (More)

Protein conformational switches have many useful applications but are difficult to design rationally. Here we demonstrate how the isoenergetic energy landscape of higher-order coiled coils can enable the formation of an oligomerization switch by insertion of a single destabilizing element into an otherwise stable computationally designed scaffold. We describe a de novo designed peptide that was discovered to switch between a parallel symmetric pentamer at pH 8 and a trimer of antiparallel dimers at pH 6. The transition between pentamer and hexamer is caused by changes in the protonation states of glutamatic acid residues with highly upshifted pKa values in both oligomer forms. The drastic conformational change coupled with the narrow pH range makes the peptide sequence an attractive candidate for introduction of pH sensing into other proteins. The results highlight the remarkable ability of simple-α helices to self-assemble into a vast range of structural states.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Structure
volume
24
issue
6
pages
10 pages
publisher
Cell Press
external identifiers
  • pmid:27161978
  • wos:000377782200015
  • scopus:84964931665
ISSN
0969-2126
DOI
10.1016/j.str.2016.03.027
language
English
LU publication?
yes
id
830c5b6f-4fec-4218-98f3-636e9dbcdd74
date added to LUP
2016-07-19 08:37:54
date last changed
2024-10-24 02:44:43
@article{830c5b6f-4fec-4218-98f3-636e9dbcdd74,
  abstract     = {{<p>Protein conformational switches have many useful applications but are difficult to design rationally. Here we demonstrate how the isoenergetic energy landscape of higher-order coiled coils can enable the formation of an oligomerization switch by insertion of a single destabilizing element into an otherwise stable computationally designed scaffold. We describe a de novo designed peptide that was discovered to switch between a parallel symmetric pentamer at pH 8 and a trimer of antiparallel dimers at pH 6. The transition between pentamer and hexamer is caused by changes in the protonation states of glutamatic acid residues with highly upshifted pK<sub>a</sub> values in both oligomer forms. The drastic conformational change coupled with the narrow pH range makes the peptide sequence an attractive candidate for introduction of pH sensing into other proteins. The results highlight the remarkable ability of simple-α helices to self-assemble into a vast range of structural states.</p>}},
  author       = {{LIZATOVIC, ROBERT and Aurelius, Oskar and Stenström, Olof and Drakenberg, Torbjörn and Akke, Mikael and Logan, Derek T. and André, Ingemar}},
  issn         = {{0969-2126}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{946--955}},
  publisher    = {{Cell Press}},
  series       = {{Structure}},
  title        = {{A de Novo Designed Coiled-Coil Peptide with a Reversible pH-Induced Oligomerization Switch}},
  url          = {{http://dx.doi.org/10.1016/j.str.2016.03.027}},
  doi          = {{10.1016/j.str.2016.03.027}},
  volume       = {{24}},
  year         = {{2016}},
}