Change search
ReferencesLink to record
Permanent link

Direct link
Membrane Proteins Diffuse as Dynamic Complexes with Lipids
VTT Technical Research Center of Finland, Espoo, Finland.
VTT Technical Research Center of Finland, Espoo, Finland.
Aalto University School of Science and Engineering, Finland.
Tampere University of Technology.Finland.
Show others and affiliations
2010 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 132, no 22, 7574-+ p.Article in journal (Refereed) Published
Abstract [en]

We describe how membrane proteins diffuse laterally in the membrane plane together with the lipids surrounding them. We find a number of intriguing phenomena. The lateral displacements of the protein and the lipids are strongly correlated, as the protein and the neighboring lipids form a dynamical protein-lipid complex, consisting of similar to 50-100 lipids. The diffusion of the lipids in the complex is much slower compared to the rest of the lipids. We also find a strong directional correlation between the movements of the protein and the lipids in its vicinity. The results imply that in crowded membrane environments there are no ""free"" lipids, as they are all influenced by the protein structure and dynamics. Our results indicate that, in studies of cell membranes, protein and lipid dynamics have to be considered together.

Place, publisher, year, edition, pages
American Chemical Society , 2010. Vol. 132, no 22, 7574-+ p.
National Category
Chemical Sciences
URN: urn:nbn:se:su:diva-50526DOI: 10.1021/ja101481bISI: 000278837100005OAI: diva2:381629
authorCount :8Available from: 2010-12-28 Created: 2010-12-28 Last updated: 2011-11-02Bibliographically approved
In thesis
1. Modeling of voltage-gated ion channels
Open this publication in new window or tab >>Modeling of voltage-gated ion channels
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The recent determination of several crystal structures of voltage-gated ion channels has catalyzed computational efforts of studying these remarkable molecular machines that are able to conduct ions across biological membranes at extremely high rates without compromising the ion selectivity.

Starting from the open crystal structures, we have studied the gating mechanism of these channels by molecular modeling techniques. Firstly, by applying a membrane potential, initial stages of the closing of the channel were captured, manifested in a secondary-structure change in the voltage-sensor. In a follow-up study, we found that the energetic cost of translocating this 310-helix conformation was significantly lower than in the original conformation. Thirdly, collaborators of ours identified new molecular constraints for different states along the gating pathway. We used those to build new protein models that were evaluated by simulations. All these results point to a gating mechanism where the S4 helix undergoes a secondary structure transformation during gating.

These simulations also provide information about how the protein interacts with the surrounding membrane. In particular, we found that lipid molecules close to the protein diffuse together with it, forming a large dynamic lipid-protein cluster. This has important consequences for the understanding of protein-membrane interactions and for the theories of lateral diffusion of membrane proteins.

Further, simulations of the simple ion channel antiamoebin were performed where different molecular models of the channel were evaluated by calculating ion conduction rates, which were compared to experimentally measured values. One of the models had a conductance consistent with the experimental data and was proposed to represent the biological active state of the channel.

Finally, the underlying methods for simulating molecular systems were probed by implementing the CHARMM force field into the GROMACS simulation package. The implementation was verified and specific GROMACS-features were combined with CHARMM and evaluated on long timescales. The CHARMM interaction potential was found to sample relevant protein conformations indifferently of the model of solvent used.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics. Stockholm University, 2011. 65 p.
Molecular modeling, Molecular dynamics, Voltage-gating, Ion channels, Protein structure prediction
National Category
Theoretical Chemistry Bioinformatics (Computational Biology)
Research subject
Biochemistry with Emphasis on Theoretical Chemistry
urn:nbn:se:su:diva-63437 (URN)978-91-7447-336-0 (ISBN)
Public defence
2011-12-16, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.Available from: 2011-11-24 Created: 2011-10-18 Last updated: 2011-11-23Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Bjelkmar, PärMurtola, TeemuLindahl, Erik
By organisation
Department of Biochemistry and Biophysics
In the same journal
Journal of the American Chemical Society
Chemical Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 33 hits
ReferencesLink to record
Permanent link

Direct link