An interdomain sector mediating allostery in Hsp70 molecular chaperones
Abstract Allosteric coupling between protein domains is fundamental to many cellular processes. For example, Hsp70 molecular chaperones use ATP binding by their actin‐like N‐terminal ATPase domain to control substrate interactions in their C‐terminal substrate‐binding domain, a reaction that is crit...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2010-09-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2010.65 |
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| _version_ | 1849225787101675520 |
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| author | Robert G Smock Olivier Rivoire William P Russ Joanna F Swain Stanislas Leibler Rama Ranganathan Lila M Gierasch |
| author_facet | Robert G Smock Olivier Rivoire William P Russ Joanna F Swain Stanislas Leibler Rama Ranganathan Lila M Gierasch |
| author_sort | Robert G Smock |
| collection | DOAJ |
| description | Abstract Allosteric coupling between protein domains is fundamental to many cellular processes. For example, Hsp70 molecular chaperones use ATP binding by their actin‐like N‐terminal ATPase domain to control substrate interactions in their C‐terminal substrate‐binding domain, a reaction that is critical for protein folding in cells. Here, we generalize the statistical coupling analysis to simultaneously evaluate co‐evolution between protein residues and functional divergence between sequences in protein sub‐families. Applying this method in the Hsp70/110 protein family, we identify a sparse but structurally contiguous group of co‐evolving residues called a ‘sector’, which is an attribute of the allosteric Hsp70 sub‐family that links the functional sites of the two domains across a specific interdomain interface. Mutagenesis of Escherichia coli DnaK supports the conclusion that this interdomain sector underlies the allosteric coupling in this protein family. The identification of the Hsp70 sector provides a basis for further experiments to understand the mechanism of allostery and introduces the idea that cooperativity between interacting proteins or protein domains can be mediated by shared sectors. |
| format | Article |
| id | doaj-art-b2ba0e6b5cfe4e2a91bd8ce9f67a48bb |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2010-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-b2ba0e6b5cfe4e2a91bd8ce9f67a48bb2025-08-24T11:59:48ZengSpringer NatureMolecular Systems Biology1744-42922010-09-016111010.1038/msb.2010.65An interdomain sector mediating allostery in Hsp70 molecular chaperonesRobert G Smock0Olivier Rivoire1William P Russ2Joanna F Swain3Stanislas Leibler4Rama Ranganathan5Lila M Gierasch6Department of Biochemistry and Molecular Biology, University of MassachusettsLaboratory of Living Matter, Rockefeller UniversityDepartment of Pharmacology and Green Center for Systems Biology, University of Texas Southwestern Medical CenterDepartment of Biochemistry and Molecular Biology, University of MassachusettsLaboratory of Living Matter, Rockefeller UniversityDepartment of Pharmacology and Green Center for Systems Biology, University of Texas Southwestern Medical CenterDepartment of Biochemistry and Molecular Biology, University of MassachusettsAbstract Allosteric coupling between protein domains is fundamental to many cellular processes. For example, Hsp70 molecular chaperones use ATP binding by their actin‐like N‐terminal ATPase domain to control substrate interactions in their C‐terminal substrate‐binding domain, a reaction that is critical for protein folding in cells. Here, we generalize the statistical coupling analysis to simultaneously evaluate co‐evolution between protein residues and functional divergence between sequences in protein sub‐families. Applying this method in the Hsp70/110 protein family, we identify a sparse but structurally contiguous group of co‐evolving residues called a ‘sector’, which is an attribute of the allosteric Hsp70 sub‐family that links the functional sites of the two domains across a specific interdomain interface. Mutagenesis of Escherichia coli DnaK supports the conclusion that this interdomain sector underlies the allosteric coupling in this protein family. The identification of the Hsp70 sector provides a basis for further experiments to understand the mechanism of allostery and introduces the idea that cooperativity between interacting proteins or protein domains can be mediated by shared sectors.https://doi.org/10.1038/msb.2010.65allosterychaperoneco‐evolutionSCAsector |
| spellingShingle | Robert G Smock Olivier Rivoire William P Russ Joanna F Swain Stanislas Leibler Rama Ranganathan Lila M Gierasch An interdomain sector mediating allostery in Hsp70 molecular chaperones Molecular Systems Biology allostery chaperone co‐evolution SCA sector |
| title | An interdomain sector mediating allostery in Hsp70 molecular chaperones |
| title_full | An interdomain sector mediating allostery in Hsp70 molecular chaperones |
| title_fullStr | An interdomain sector mediating allostery in Hsp70 molecular chaperones |
| title_full_unstemmed | An interdomain sector mediating allostery in Hsp70 molecular chaperones |
| title_short | An interdomain sector mediating allostery in Hsp70 molecular chaperones |
| title_sort | interdomain sector mediating allostery in hsp70 molecular chaperones |
| topic | allostery chaperone co‐evolution SCA sector |
| url | https://doi.org/10.1038/msb.2010.65 |
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