A conserved P-loop anchor limits the structural dynamics that mediate nucleotide dissociation in EF-Tu

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dc.contributor.authorMercier, Evan
dc.contributor.authorGirodat, Dylan
dc.contributor.authorWieden, Hans-Joachim
dc.date.accessioned2020-02-13T22:27:18Z
dc.date.available2020-02-13T22:27:18Z
dc.date.issued2015
dc.descriptionSherpa Romeo green journal. Open access article. Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (CC BY-NC-SA 4.0) applies.en_US
dc.description.abstractThe phosphate-binding loop (P-loop) is a conserved sequence motif found in mononucleotide-binding proteins. Little is known about the structural dynamics of this region and its contribution to the observed nucleotide binding properties. Understanding the underlying design principles is of great interest for biomolecular engineering applications. We have used rapid-kinetics measurements in vitro and molecular dynamics (MD) simulations in silico to investigate the relationship between GTP-binding properties and P-loop structural dynamics in the universally conserved Elongation Factor (EF) Tu. Analysis of wild type EF-Tu and variants with substitutions at positions in or adjacent to the P-loop revealed a correlation between P-loop flexibility and the entropy of activation for GTP dissociation. The same variants demonstrate more backbone flexibility in two N-terminal amino acids of the P-loop during force-induced EF-Tu-GTP dissociation in Steered Molecular Dynamics simulations. Amino acids Gly18 and His19 are involved in stabilizing the P-loop backbone via interactions with the adjacent helix C.We propose that these P-loop/helix C interactions function as a conserved P-loop anchoring module and identify the presence of P-loop anchors within several GTPases and ATPases suggesting their evolutionary conservation.en_US
dc.description.peer-reviewYesen_US
dc.identifier.citationMercier, E., Girodat, D., & Wieden, H.-J. (2015). A conserved P-loop anchor limits the structural dynamics that mediate nucleotide dissociation in EF-Tu. Scientific Report, 5, 7677. https://doi.org/10.1038/srep07677en_US
dc.identifier.urihttps://hdl.handle.net/10133/5678
dc.language.isoen_USen_US
dc.publisherNature Researchen_US
dc.publisher.departmentDepartment of Chemistry and Biochemistryen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.urlhttps://doi.org/10.1038/srep07677
dc.subjectPhosphate-binding loop
dc.subjectP-loop
dc.subjectNucleotide
dc.subjectGTP
dc.subjectEF-Tu
dc.subjectBiomolecular engineering
dc.subjectKinetics
dc.subjectTranslation
dc.subject.lcshChemical kinetics
dc.titleA conserved P-loop anchor limits the structural dynamics that mediate nucleotide dissociation in EF-Tuen_US
dc.typeArticleen_US
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