Evolutionary adaptation of the protein folding pathway for secretability
| Autor: | Dries Smets, Alexandra Tsirigotaki, Jochem H Smit, Srinath Krishnamurthy, Athina G Portaliou, Anastassia Vorobieva, Wim Vranken, Spyridoula Karamanou, Anastassios Economou |
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| Přispěvatelé: | Structural Biology Brussels, Department of Bio-engineering Sciences, Basic (bio-) Medical Sciences, Chemistry, Informatics and Applied Informatics |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
folding
Protein Folding General Immunology and Microbiology General Neuroscience Cell Membrane mature domain Proteins Protein Sorting Signals General Biochemistry Genetics and Molecular Biology secretion Immunology and Microbiology(all) signal peptide HDX-MS Hydrophobic and Hydrophilic Interactions Molecular Biology |
| Popis: | Secretory preproteins of the Sec pathway are targeted post-translationally and cross cellular membranes through translocases. During cytoplasmic transit, mature domains remain non-folded for translocase recognition/translocation. After translocation and signal peptide cleavage, mature domains fold to native states in the bacterial periplasm or traffic further. We sought the structural basis for delayed mature domain folding and how signal peptides regulate it. We compared how evolution diversified a periplasmic peptidyl-prolyl isomerase PpiA mature domain from its structural cytoplasmic PpiB twin. Global and local hydrogen-deuterium exchange mass spectrometry showed that PpiA is a slower folder. We defined at near-residue resolution hierarchical folding initiated by similar foldons in the twins, at different order and rates. PpiA folding is delayed by less hydrophobic native contacts, frustrated residues and a β-turn in the earliest foldon and by signal peptide-mediated disruption of foldon hierarchy. When selected PpiA residues and/or its signal peptide were grafted onto PpiB, they converted it into a slow folder with enhanced in vivo secretion. These structural adaptations in a secretory protein facilitate trafficking. ispartof: EMBO JOURNAL vol:41 issue:23 ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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