Change search
ReferencesLink to record
Permanent link

Direct link
Coils in the membrane core are conserved and functionally important
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.ORCID iD: 0000-0002-7115-9751
2008 (English)In: Journal of Molecular Biology, ISSN 0022-2836, Vol. 380, no 1, 170-180 p.Article in journal (Refereed) Published
Abstract [en]

With the increasing number of available α-helical transmembrane (TM) protein structures, the traditional picture of membrane proteins has been challenged. For example, reentrant regions, which enter and exit the membrane at the same side, and interface helices, which lie parallel with the membrane in the membrane–water interface, are common. Furthermore, TM helices are frequently kinked, and their length and tilt angle vary. Here, we systematically analyze 7% of all residues within the deep membrane core that are in coil state. These coils can be found in TM-helix kinks as major breaks in TM helices and as parts of reentrant regions.

Coil residues are significantly more conserved than other residues. Due to the polar character of the coil backbone, they are either buried or located near aqueous channels. Coil residues are frequently found within channels and transporters, where they introduce the flexibility and polarity required for transport across the membrane. Therefore, we believe that coil residues in the membrane core, while constituting a structural anomaly, are essential for the function of proteins.

Place, publisher, year, edition, pages
2008. Vol. 380, no 1, 170-180 p.
Keyword [en]
Amino Acid Sequence, Amino Acid Substitution, Conserved Sequence, Hydrogen Bonding, Ion Channels/chemistry, Membrane Proteins/*chemistry/*metabolism, Membrane Transport Proteins/chemistry, Models; Molecular, Protein Structure; Secondary, Software, Structure-Activity Relationship
URN: urn:nbn:se:su:diva-14856DOI: 10.1016/j.jmb.2008.04.052ISI: 000257469600014PubMedID: 18511074OAI: diva2:181376
Available from: 2008-11-20 Created: 2008-11-20 Last updated: 2014-11-10Bibliographically approved
In thesis
1. On the effects of structure and function on protein evolution
Open this publication in new window or tab >>On the effects of structure and function on protein evolution
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Many proteins can be described as working machines that make sure that everything functions in the cell. Their specific molecular functions are largely dependent on their three-dimensional structures, which in turn are mainly predetermined by their linear sequences of amino acid residues. Therefore, there is a relation between the sequence, structure and function of a protein, in which knowledge about the structure is crucial for understanding the functions. The structure is generally difficult to determine experimentally, but should in principle be possible to predict from the sequence by computational methods. The instructions of how to build the linear proteins sequences are copied during cell division and are passed on to successive generations. Although the copying process is a very efficient and accurate system, it does not function correctly on every occasion. Sometimes errors, or mutations can result from the process. These mutations gradually accumulate over time, so that the sequences and thereby also the structures and functions of proteins evolve overtime. This thesis is based on four papers concerning the relationship between function, structure and sequence and how it changes during the evolution of proteins. Paper I shows that the structural change is linearly related to sequence change and that structures are 3 to 10 times more conserved than sequences. In Paper II and Paper III we investigated non-helical structures and polar residues, respectively, positioned in the nonpolar membrane core environment of α-helical membrane proteins. Both types were found to be evolutionary conserved and functionally important. Paper IV includes the development of a method to predict the residues in α-helical membrane proteins that after folding become exposed to the solvent environment.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2010. 48 p.
protein, structure, function, evolution, membrane
National Category
Biochemistry and Molecular Biology
Research subject
urn:nbn:se:su:diva-35872 (URN)978-91-7155-980-7 (ISBN)
Public defence
2010-02-19, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.Available from: 2010-01-28 Created: 2010-01-20 Last updated: 2014-11-10Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Illergård, KristofferElofsson, Arne
By organisation
Department of Biochemistry and Biophysics
In the same journal
Journal of Molecular Biology

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: 32 hits
ReferencesLink to record
Permanent link

Direct link