Show simple item record

dc.contributor.authorMarsden, Andrew P
dc.contributor.authorHollins, Jeffrey J
dc.contributor.authorO'Neill, Charles
dc.contributor.authorRyzhov, Pavel
dc.contributor.authorHigson, Sally
dc.contributor.authorMendonça, Carolina ATF
dc.contributor.authorKwan, Tristan O
dc.contributor.authorKwa, Lee Gyan
dc.contributor.authorSteward, Annette
dc.contributor.authorClarke, Jane
dc.date.accessioned2018-12-12T00:31:41Z
dc.date.available2018-12-12T00:31:41Z
dc.date.issued2018-12-07
dc.identifier.issn0022-2836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286725
dc.description.abstractDetermining the relationship between protein folding pathways on and off the ribosome remains an important area of investigation in biology. Studies on isolated domains have shown that alteration of the separation of residues in a polypeptide chain, while maintaining their spatial contacts, may affect protein stability and folding pathway. Due to the vectorial emergence of the polypeptide chain from the ribosome, chain connectivity may have an important influence upon cotranslational folding. Using MATH, an all β-sandwich domain, we investigate whether the connectivity of residues and secondary structure elements is a key determinant of when cotranslational folding can occur on the ribosome. From Φ-value analysis, we show that the most structured region of the transition state for folding in MATH includes the N and C terminal strands, which are located adjacent to each other in the structure. However, arrest peptide force-profile assays show that wild-type MATH is able to fold cotranslationally, while some C-terminal residues remain sequestered in the ribosome, even when destabilized by 2-3 kcal mol-1. We show that, while this pattern of Φ-values is retained in two circular permutants in our studies of the isolated domains, one of these permutants can fold only when fully emerged from the ribosome. We propose that in the case of MATH, onset of cotranslational folding is determined by the ability to form a sufficiently stable folding nucleus involving both β-sheets, rather than by the location of the terminal strands in the ribosome tunnel.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectRibosomes
dc.subjectTumor Necrosis Factor Receptor-Associated Peptides and Proteins
dc.subjectProtein Biosynthesis
dc.subjectProtein Structure, Secondary
dc.subjectProtein Folding
dc.subjectKinetics
dc.subjectModels, Molecular
dc.subjectProtein Stability
dc.subjectProtein Conformation, beta-Strand
dc.titleInvestigating the Effect of Chain Connectivity on the Folding of a Beta-Sheet Protein On and Off the Ribosome.
dc.typeArticle
prism.endingPage5216
prism.issueIdentifier24
prism.publicationDate2018
prism.publicationNameJ Mol Biol
prism.startingPage5207
prism.volume430
dc.identifier.doi10.17863/CAM.34032
dcterms.dateAccepted2018-10-16
rioxxterms.versionofrecord10.1016/j.jmb.2018.10.011
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-12
dc.contributor.orcidClarke, Jane [0000-0002-7921-900X]
dc.identifier.eissn1089-8638
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (095195/Z/10/Z)
cam.issuedOnline2018-10-23


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International