Header

UZH-Logo

Maintenance Infos

Strategies for Selection from Protein Libraries Composed of de Novo Designed Secondary Structure Modules


Matsuura, Tomoaki; Plückthun, Andreas (2004). Strategies for Selection from Protein Libraries Composed of de Novo Designed Secondary Structure Modules. Origins of Life and Evolution of the Biosphere, 34(1/2):151-157.

Abstract

As more and more protein structures are determined, it has become clear that there is only a limited number of protein folds in nature. To explore whether the protein folds found in nature are the only solutions to the protein folding problem, or that a lack of evolutionary pressure causes the paucity of different protein folds found, we set out to construct protein libraries without any restriction on topology. We generated different libraries (all α-helix, all β-strand and α-helix plus β-strand) with an average length of 100 amino acid residues, composed of designed secondary structure modules (α-helix, β-strand and β-turn) in various proportions, based primarily on the patterning of polar and non-polar residues. From the analysis of proteins chosen randomly from the libraries, we found that a substantial portion of pure α-helical proteins show properties similar to native proteins.Using these libraries as a starting point, we aim to establish a selection system which allows us to enrich proteins with favorable folding properties (non-aggregating, compactly folded) from the libraries. We have developed such a method based on ribosome display. This selection is based on two concepts: (1) misfolded proteins are more sensitive to proteolysis, (2) misfolded and/or aggregated proteins are more hydrophobic. We show that by applying each of these selection criteria proteins that are compactly folded and soluble can be enriched over insoluble and random coil proteins

Abstract

As more and more protein structures are determined, it has become clear that there is only a limited number of protein folds in nature. To explore whether the protein folds found in nature are the only solutions to the protein folding problem, or that a lack of evolutionary pressure causes the paucity of different protein folds found, we set out to construct protein libraries without any restriction on topology. We generated different libraries (all α-helix, all β-strand and α-helix plus β-strand) with an average length of 100 amino acid residues, composed of designed secondary structure modules (α-helix, β-strand and β-turn) in various proportions, based primarily on the patterning of polar and non-polar residues. From the analysis of proteins chosen randomly from the libraries, we found that a substantial portion of pure α-helical proteins show properties similar to native proteins.Using these libraries as a starting point, we aim to establish a selection system which allows us to enrich proteins with favorable folding properties (non-aggregating, compactly folded) from the libraries. We have developed such a method based on ribosome display. This selection is based on two concepts: (1) misfolded proteins are more sensitive to proteolysis, (2) misfolded and/or aggregated proteins are more hydrophobic. We show that by applying each of these selection criteria proteins that are compactly folded and soluble can be enriched over insoluble and random coil proteins

Statistics

Citations

Dimensions.ai Metrics
8 citations in Web of Science®
13 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

13 downloads since deposited on 19 Oct 2018
10 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:Unspecified
Scopus Subject Areas:Life Sciences > Ecology, Evolution, Behavior and Systematics
Physical Sciences > Space and Planetary Science
Language:English
Date:1 February 2004
Deposited On:19 Oct 2018 12:34
Last Modified:31 Jul 2020 02:48
Publisher:Springer
ISSN:0169-6149
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1023/b:orig.0000009836.86519.eb
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicencespringer101023BORIG000000983686519eb (Library Catalogue)

Download

Green Open Access

Download PDF  'Strategies for Selection from Protein Libraries Composed of de Novo Designed Secondary Structure Modules'.
Preview
Content: Published Version
Language: English
Filetype: PDF (Nationallizenz 142-005)
Size: 92kB
View at publisher