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 |
|