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Knots can impair protein degradation by ATP-dependent proteases

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dc.contributor.author San Martín, Álvaro
dc.contributor.author Rodriguez-Aliaga, Piere
dc.contributor.author Molina, José Alejandro
dc.contributor.author Martin, Andreas
dc.contributor.author Bustamante, Carlos
dc.contributor.author Baez, Mauricio
dc.date.accessioned 2019-01-25T15:28:04Z
dc.date.available 2019-01-25T15:28:04Z
dc.date.issued 2017
dc.identifier.uri https://hdl.handle.net/20.500.12866/4686
dc.description.abstract ATP-dependent proteases translocate proteins through a narrow pore for their controlled destruction. However, how a protein substrate containing a knotted topology affects this process remains unknown. Here, we characterized the effects of the trefoil-knotted protein MJ0366 from Methanocaldococcus jannaschii on the operation of the ClpXP protease from Escherichia coli ClpXP completely degrades MJ0366 when pulling from the C-terminal ssrA-tag. However, when a GFP moiety is appended to the N terminus of MJ0366, ClpXP releases intact GFP with a 47-residue tail. The extended length of this tail suggests that ClpXP tightens the trefoil knot against GFP, which prevents GFP unfolding. Interestingly, if the linker between the knot core of MJ0366 and GFP is longer than 36 residues, ClpXP tightens and translocates the knot before it reaches GFP, enabling the complete unfolding and degradation of the substrate. These observations suggest that a knot-induced stall during degradation of multidomain proteins by AAA proteases may constitute a novel mechanism to produce partially degraded products with potentially new functions. en_US
dc.language.iso eng
dc.publisher National Academy of Sciences
dc.relation.ispartofseries Proceedings of the National Academy of Sciences of the United States of America
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject AAA+ ATPase en_US
dc.subject knot translocation en_US
dc.subject knotted protein en_US
dc.subject protein degradation en_US
dc.subject Protein Folding en_US
dc.subject Proteolysis en_US
dc.subject translocation arrest en_US
dc.subject Endopeptidase Clp/metabolism en_US
dc.subject Green Fluorescent Proteins/genetics en_US
dc.subject Homeodomain Proteins/metabolism en_US
dc.subject Methanocaldococcus/genetics en_US
dc.subject Protein Transport/physiology en_US
dc.subject Protein Unfolding en_US
dc.subject Thermodynamics en_US
dc.title Knots can impair protein degradation by ATP-dependent proteases en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1073/pnas.1705916114
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.03
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.01
dc.relation.issn 1091-6490

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