The ‘Shape-Shifter’ Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational Preferences
Multiple crystal structures of the homo-trimeric protein disulphide isomerase PmScsC reveal that the peptide which links the trimerization stalk and catalytic domain can adopt helical, β-strand and loop conformations. This region has been called a ‘shape-shifter’ peptide. Characterisation of this pe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/11/5/642 |
| _version_ | 1797536189684645888 |
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| author | Lorna J. Smith Chloe W. Green Christina Redfield |
| author_facet | Lorna J. Smith Chloe W. Green Christina Redfield |
| author_sort | Lorna J. Smith |
| collection | DOAJ |
| description | Multiple crystal structures of the homo-trimeric protein disulphide isomerase PmScsC reveal that the peptide which links the trimerization stalk and catalytic domain can adopt helical, β-strand and loop conformations. This region has been called a ‘shape-shifter’ peptide. Characterisation of this peptide using NMR experiments and MD simulations has shown that it is essentially disordered in solution. Analysis of the PmScsC crystal structures identifies the role of intermolecular contacts, within an assembly of protein molecules, in stabilising the different linker peptide conformations. These context-dependent conformational properties may be important functionally, allowing for the binding and disulphide shuffling of a variety of protein substrates to PmScsC. They also have a relevance for our understanding of protein aggregation and misfolding showing how intermolecular quaternary interactions can lead to β-sheet formation by a sequence that in other contexts adopts a helical structure. This ‘shape-shifting’ peptide region within PmScsC is reminiscent of one-to-many molecular recognition features (MoRFs) found in intrinsically disordered proteins which are able to adopt different conformations when they fold upon binding to their protein partners. |
| first_indexed | 2024-03-10T11:57:10Z |
| format | Article |
| id | doaj.art-8ac3ed547d4e4d4b90fa2ef03a0d20f6 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T11:57:10Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-8ac3ed547d4e4d4b90fa2ef03a0d20f62023-11-21T17:15:33ZengMDPI AGBiomolecules2218-273X2021-04-0111564210.3390/biom11050642The ‘Shape-Shifter’ Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational PreferencesLorna J. Smith0Chloe W. Green1Christina Redfield2Department of Chemistry, University of Oxford, Oxford OX1 3QR, UKDepartment of Chemistry, University of Oxford, Oxford OX1 3QR, UKDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UKMultiple crystal structures of the homo-trimeric protein disulphide isomerase PmScsC reveal that the peptide which links the trimerization stalk and catalytic domain can adopt helical, β-strand and loop conformations. This region has been called a ‘shape-shifter’ peptide. Characterisation of this peptide using NMR experiments and MD simulations has shown that it is essentially disordered in solution. Analysis of the PmScsC crystal structures identifies the role of intermolecular contacts, within an assembly of protein molecules, in stabilising the different linker peptide conformations. These context-dependent conformational properties may be important functionally, allowing for the binding and disulphide shuffling of a variety of protein substrates to PmScsC. They also have a relevance for our understanding of protein aggregation and misfolding showing how intermolecular quaternary interactions can lead to β-sheet formation by a sequence that in other contexts adopts a helical structure. This ‘shape-shifting’ peptide region within PmScsC is reminiscent of one-to-many molecular recognition features (MoRFs) found in intrinsically disordered proteins which are able to adopt different conformations when they fold upon binding to their protein partners.https://www.mdpi.com/2218-273X/11/5/642NMR spectroscopyMD simulationX-ray crystallographyprotein dynamicschameleon sequenceprotein folding |
| spellingShingle | Lorna J. Smith Chloe W. Green Christina Redfield The ‘Shape-Shifter’ Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational Preferences Biomolecules NMR spectroscopy MD simulation X-ray crystallography protein dynamics chameleon sequence protein folding |
| title | The ‘Shape-Shifter’ Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational Preferences |
| title_full | The ‘Shape-Shifter’ Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational Preferences |
| title_fullStr | The ‘Shape-Shifter’ Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational Preferences |
| title_full_unstemmed | The ‘Shape-Shifter’ Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational Preferences |
| title_short | The ‘Shape-Shifter’ Peptide from the Disulphide Isomerase PmScsC Shows Context-Dependent Conformational Preferences |
| title_sort | shape shifter peptide from the disulphide isomerase pmscsc shows context dependent conformational preferences |
| topic | NMR spectroscopy MD simulation X-ray crystallography protein dynamics chameleon sequence protein folding |
| url | https://www.mdpi.com/2218-273X/11/5/642 |
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