The linker pivot in Ci-VSP: the key to unlock catalysis.
In the voltage-sensitive phosphatase Ci-VSP, conformational changes in the transmembrane voltage sensor domain (VSD) are transduced to the intracellular catalytic domain (CD) leading to its dephosphorylation activity against membrane-embedded phosphoinositides. The linker between both domains is pro...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3726396?pdf=render |
| _version_ | 1811335909284511744 |
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| author | Kirstin Hobiger Tillmann Utesch Maria Andrea Mroginski Guiscard Seebohm Thomas Friedrich |
| author_facet | Kirstin Hobiger Tillmann Utesch Maria Andrea Mroginski Guiscard Seebohm Thomas Friedrich |
| author_sort | Kirstin Hobiger |
| collection | DOAJ |
| description | In the voltage-sensitive phosphatase Ci-VSP, conformational changes in the transmembrane voltage sensor domain (VSD) are transduced to the intracellular catalytic domain (CD) leading to its dephosphorylation activity against membrane-embedded phosphoinositides. The linker between both domains is proposed to be crucial for the VSD-CD coupling. With a combined approach of electrophysiological measurements on Xenopus oocytes and molecular dynamics simulations of a Ci-VSP model embedded in a lipid bilayer, we analyzed how conformational changes in the linker mediate the interaction between the CD and the activated VSD. In this way, we identified specific residues in the linker that interact with well-defined amino acids in one of the three loops forming the active site of the protein, named TI loop. With our results, we shed light into the early steps of the coupling process between the VSD and the CD, which are based on fine-tuned electrostatic and hydrophobic interactions between the linker, the membrane and the CD. |
| first_indexed | 2024-04-13T17:31:35Z |
| format | Article |
| id | doaj.art-903b7ff1f7bb4af9b01c3c273b33bda8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T17:31:35Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-903b7ff1f7bb4af9b01c3c273b33bda82022-12-22T02:37:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e7027210.1371/journal.pone.0070272The linker pivot in Ci-VSP: the key to unlock catalysis.Kirstin HobigerTillmann UteschMaria Andrea MroginskiGuiscard SeebohmThomas FriedrichIn the voltage-sensitive phosphatase Ci-VSP, conformational changes in the transmembrane voltage sensor domain (VSD) are transduced to the intracellular catalytic domain (CD) leading to its dephosphorylation activity against membrane-embedded phosphoinositides. The linker between both domains is proposed to be crucial for the VSD-CD coupling. With a combined approach of electrophysiological measurements on Xenopus oocytes and molecular dynamics simulations of a Ci-VSP model embedded in a lipid bilayer, we analyzed how conformational changes in the linker mediate the interaction between the CD and the activated VSD. In this way, we identified specific residues in the linker that interact with well-defined amino acids in one of the three loops forming the active site of the protein, named TI loop. With our results, we shed light into the early steps of the coupling process between the VSD and the CD, which are based on fine-tuned electrostatic and hydrophobic interactions between the linker, the membrane and the CD.http://europepmc.org/articles/PMC3726396?pdf=render |
| spellingShingle | Kirstin Hobiger Tillmann Utesch Maria Andrea Mroginski Guiscard Seebohm Thomas Friedrich The linker pivot in Ci-VSP: the key to unlock catalysis. PLoS ONE |
| title | The linker pivot in Ci-VSP: the key to unlock catalysis. |
| title_full | The linker pivot in Ci-VSP: the key to unlock catalysis. |
| title_fullStr | The linker pivot in Ci-VSP: the key to unlock catalysis. |
| title_full_unstemmed | The linker pivot in Ci-VSP: the key to unlock catalysis. |
| title_short | The linker pivot in Ci-VSP: the key to unlock catalysis. |
| title_sort | linker pivot in ci vsp the key to unlock catalysis |
| url | http://europepmc.org/articles/PMC3726396?pdf=render |
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