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Structure is three to ten times more conserved than sequence--a study of structural response in protein cores
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
2009 (English)In: Proteins, ISSN 0887-3585, Vol. 77, no 3, 499-508 p.Article in journal (Refereed) Published
Abstract [en]

Protein structures change during evolution in response to mutations. Here, we analyze the mapping between sequence and structure in a set of structurally aligned protein domains. To avoid artifacts, we restricted our attention only to the core components of these structures. We found that on average, using different measures of structural change, protein cores evolve linearly with evolutionary distance (amino acid substitutions per site). This is true irrespective of which measure of structural change we used, whether RMSD or discrete structural descriptors for secondary structure, accessibility, or contacts. This linear response allows us to quantify the claim that structure is more conserved than sequence. Using structural alphabets of similar cardinality to the sequence alphabet, structural cores evolve three to ten times slower than sequences. Although we observed an average linear response, we found a wide variance. Different domain families varied fivefold in structural response to evolution. An attempt to categorically analyze this variance among subgroups by structural and functional category revealed only one statistically significant trend. This trend can be explained by the fact that beta-sheets change faster than alpha-helices, most likely due to that they are shorter and that change occurs at the ends of the secondary structure elements.

Place, publisher, year, edition, pages
2009. Vol. 77, no 3, 499-508 p.
URN: urn:nbn:se:su:diva-34574DOI: 10.1002/prot.22458ISI: 000270849900002PubMedID: 19507241OAI: diva2:285150
Available from: 2010-01-11 Created: 2010-01-11 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

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Illergård, KristofferElofsson, Arne
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