Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Changes of protein folding pathways by circular permutation. Overlapping nuclei promote global cooperativity.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. (Mikael Oliveberg)
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
2008 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 283, no 41, 27904-27915 p.Article in journal (Refereed) Published
Abstract [en]

The evolved properties of proteins are not limited to structure and stability but also include their propensity to undergo local conformational changes. The latter, dynamic property is related to structural cooperativity and is controlled by the folding-energy landscape. Here we demonstrate that the structural cooperativity of the ribosomal protein S6 is optimized by geometric overlap of two competing folding nuclei: they both include the central beta-strand 1. In this way, folding of one nucleus catalyzes the formation of the other, contributing to make the folding transition more concerted overall. The experimental evidence is provided by an extended set of circular permutations of S6 that allows quantitative analysis of pathway plasticity at the level of individual side chains. Because similar overlap between competing nuclei also has been discerned in other proteins, we hypothesize that the coupling of several small nuclei into extended "supernuclei" represents a general principle for propagating folding cooperativity across large structural distances.

Place, publisher, year, edition, pages
2008. Vol. 283, no 41, 27904-27915 p.
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:su:diva-29978DOI: 10.1074/jbc.M801776200ISI: 000259719200061OAI: oai:DiVA.org:su-29978DiVA: diva2:236870
Available from: 2009-09-25 Created: 2009-09-25 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Folding of the Ribosomal protein S6: The role of sequence connectivity, overlapping foldons, and parallel pathways
Open this publication in new window or tab >>Folding of the Ribosomal protein S6: The role of sequence connectivity, overlapping foldons, and parallel pathways
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

To investigate how protein folding is affected by sequence connectivity five topological variants of the ribosomal protein S6 were constructed through circular permutation.  In these constructs, the chain connectivity (i.e. the order of secondary-structure elements) is changed without changing the native-state topology.  The effects of the permutations on the folding process were then characterised by φ-value analysis, which estimates the extent of contact formations in the transition-state ensemble.  The results show that the folding nuclei of the wild-type and permutant proteins comprises a common motif of one α-helix docking against two β-sheets, i.e. the minimal structure for folding.  However, this motif is recruited in different parts of the S6 structure depending on the permutation, either in the α1 or α2 half of the protein.  This minimal structure is not unique for S6 but can also be seen in other proteins.  As an effect of the dual nucleation possibilities, the transition-state changes describe a competition between two parallel pathways, which both include the central β-stand 1.  This strand constitutes thus a structural overlap between the two competing nuclei.  As similar overlap between competing nuclei is also seen in other proteins, I hypothesise that the coupling of several small nuclei into extended ‘super nuclei’ represents a general principle for propagating folding cooperativity across large structural distances.  Moreover, I demonstrate by NMR analysis that the existence of multiple folding nuclei renders the H/D-exchange kinetics independent of the folding pathway.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2009. 94 p.
Keyword
protein folding, protein stability, two-state folding, S6, chevron plot, transition state, parallell pathways, foldon, two-channel landscape, protein engineering, H/D-exchange
National Category
Biochemistry and Molecular Biology
Research subject
Biochemistry
Identifiers
urn:nbn:se:su:diva-29963 (URN)978-91-7155-939-5 (ISBN)
Public defence
2009-10-24, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper IV: ManuscriptAvailable from: 2009-10-01 Created: 2009-09-23 Last updated: 2009-09-29Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textLink to Doctoral Thesis

Search in DiVA

By author/editor
Haglund, EllinorOliveberg, Mikael
By organisation
Department of Biochemistry and Biophysics
In the same journal
Journal of Biological Chemistry
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 68 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf