The peripheral binding of 14-3-3γ to membranes involves isoform-specific histidine residues.
Mammalian 14-3-3 protein scaffolds include seven conserved isoforms that bind numerous phosphorylated protein partners and regulate many cellular processes. Some 14-3-3-isoforms, notably γ, have elevated affinity for membranes, which might contribute to modulate the subcellular localization of the p...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2012
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/0bbdece711e542388e84f0510ac60920 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:0bbdece711e542388e84f0510ac60920 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:0bbdece711e542388e84f0510ac609202021-11-18T08:07:38ZThe peripheral binding of 14-3-3γ to membranes involves isoform-specific histidine residues.1932-620310.1371/journal.pone.0049671https://doaj.org/article/0bbdece711e542388e84f0510ac609202012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23189152/?tool=EBIhttps://doaj.org/toc/1932-6203Mammalian 14-3-3 protein scaffolds include seven conserved isoforms that bind numerous phosphorylated protein partners and regulate many cellular processes. Some 14-3-3-isoforms, notably γ, have elevated affinity for membranes, which might contribute to modulate the subcellular localization of the partners and substantiate the importance of investigating molecular mechanisms of membrane interaction. By applying surface plasmon resonance we here show that the binding to phospholipid bilayers is stimulated when 14-3-3γ is complexed with its partner, a peptide corresponding to the Ser19-phosphorylated N-terminal region of tyrosine hydroxylase. Moreover, membrane interaction is dependent on salts of kosmotropic ions, which also stabilize 14-3-3γ. Electrostatic analysis of available crystal structures of γ and of the non-membrane-binding ζ-isoform, complemented with molecular dynamics simulations, indicate that the electrostatic potential distribution of phosphopeptide-bound 14-3-3γ is optimal for interaction with the membrane through amphipathic helices at the N-terminal dimerization region. In addition, His158, and especially His195, both specific to 14-3-3γ and located at the convex lateral side, appeared to be pivotal for the ligand induced membrane interaction, as corroborated by site-directed mutagenesis. The participation of these histidine residues might be associated to their increased protonation upon membrane binding. Overall, these results reveal membrane-targeting motifs and give insights on mechanisms that furnish the 14-3-3γ scaffold with the capacity for tuned shuffling from soluble to membrane-bound states.Helene J BustadLars SkjaervenMing YingØyvind HalskauAnne BaumannDavid Rodriguez-LarreaMiguel CostasJarl UnderhaugJose M Sanchez-RuizAurora MartinezPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49671 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Helene J Bustad Lars Skjaerven Ming Ying Øyvind Halskau Anne Baumann David Rodriguez-Larrea Miguel Costas Jarl Underhaug Jose M Sanchez-Ruiz Aurora Martinez The peripheral binding of 14-3-3γ to membranes involves isoform-specific histidine residues. |
| description |
Mammalian 14-3-3 protein scaffolds include seven conserved isoforms that bind numerous phosphorylated protein partners and regulate many cellular processes. Some 14-3-3-isoforms, notably γ, have elevated affinity for membranes, which might contribute to modulate the subcellular localization of the partners and substantiate the importance of investigating molecular mechanisms of membrane interaction. By applying surface plasmon resonance we here show that the binding to phospholipid bilayers is stimulated when 14-3-3γ is complexed with its partner, a peptide corresponding to the Ser19-phosphorylated N-terminal region of tyrosine hydroxylase. Moreover, membrane interaction is dependent on salts of kosmotropic ions, which also stabilize 14-3-3γ. Electrostatic analysis of available crystal structures of γ and of the non-membrane-binding ζ-isoform, complemented with molecular dynamics simulations, indicate that the electrostatic potential distribution of phosphopeptide-bound 14-3-3γ is optimal for interaction with the membrane through amphipathic helices at the N-terminal dimerization region. In addition, His158, and especially His195, both specific to 14-3-3γ and located at the convex lateral side, appeared to be pivotal for the ligand induced membrane interaction, as corroborated by site-directed mutagenesis. The participation of these histidine residues might be associated to their increased protonation upon membrane binding. Overall, these results reveal membrane-targeting motifs and give insights on mechanisms that furnish the 14-3-3γ scaffold with the capacity for tuned shuffling from soluble to membrane-bound states. |
| format |
article |
| author |
Helene J Bustad Lars Skjaerven Ming Ying Øyvind Halskau Anne Baumann David Rodriguez-Larrea Miguel Costas Jarl Underhaug Jose M Sanchez-Ruiz Aurora Martinez |
| author_facet |
Helene J Bustad Lars Skjaerven Ming Ying Øyvind Halskau Anne Baumann David Rodriguez-Larrea Miguel Costas Jarl Underhaug Jose M Sanchez-Ruiz Aurora Martinez |
| author_sort |
Helene J Bustad |
| title |
The peripheral binding of 14-3-3γ to membranes involves isoform-specific histidine residues. |
| title_short |
The peripheral binding of 14-3-3γ to membranes involves isoform-specific histidine residues. |
| title_full |
The peripheral binding of 14-3-3γ to membranes involves isoform-specific histidine residues. |
| title_fullStr |
The peripheral binding of 14-3-3γ to membranes involves isoform-specific histidine residues. |
| title_full_unstemmed |
The peripheral binding of 14-3-3γ to membranes involves isoform-specific histidine residues. |
| title_sort |
peripheral binding of 14-3-3γ to membranes involves isoform-specific histidine residues. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/0bbdece711e542388e84f0510ac60920 |
| work_keys_str_mv |
AT helenejbustad theperipheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT larsskjaerven theperipheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT mingying theperipheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT øyvindhalskau theperipheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT annebaumann theperipheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT davidrodriguezlarrea theperipheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT miguelcostas theperipheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT jarlunderhaug theperipheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT josemsanchezruiz theperipheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT auroramartinez theperipheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT helenejbustad peripheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT larsskjaerven peripheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT mingying peripheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT øyvindhalskau peripheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT annebaumann peripheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT davidrodriguezlarrea peripheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT miguelcostas peripheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT jarlunderhaug peripheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT josemsanchezruiz peripheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues AT auroramartinez peripheralbindingof1433gtomembranesinvolvesisoformspecifichistidineresidues |
| _version_ |
1718422150438715392 |