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dc.contributor.authorHalfmann, Randal Arthur
dc.contributor.authorAlberti, Simon
dc.contributor.authorKrishnan, Rajaraman
dc.contributor.authorLyle, Nicholas
dc.contributor.authorO'Donnell, Charles William
dc.contributor.authorKing, Oliver D.
dc.contributor.authorBerger, Bonnie
dc.contributor.authorPappu, Rohit V.
dc.contributor.authorLindquist, Susan
dc.date.accessioned2014-12-16T14:29:21Z
dc.date.available2014-12-16T14:29:21Z
dc.date.issued2011-07
dc.date.submitted2011-03
dc.identifier.issn10972765
dc.identifier.issn1097-4164
dc.identifier.urihttp://hdl.handle.net/1721.1/92316
dc.description.abstractSequences rich in glutamine (Q) and asparagine (N) residues often fail to fold at the monomer level. This, coupled to their unusual hydrogen-bonding abilities, provides the driving force to switch between disordered monomers and amyloids. Such transitions govern processes as diverse as human protein-folding diseases, bacterial biofilm assembly, and the inheritance of yeast prions (protein-based genetic elements). A systematic survey of prion-forming domains suggested that Q and N residues have distinct effects on amyloid formation. Here, we use cell biological, biochemical, and computational techniques to compare Q/N-rich protein variants, replacing Ns with Qs and Qs with Ns. We find that the two residues have strong and opposing effects: N richness promotes assembly of benign self-templating amyloids; Q richness promotes formation of toxic nonamyloid conformers. Molecular simulations focusing on intrinsic folding differences between Qs and Ns suggest that their different behaviors are due to the enhanced turn-forming propensity of Ns over Qs.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant GM025874)en_US
dc.description.sponsorshipG. Harold and Leila Y. Mathers Foundationen_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.molcel.2011.05.013en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceElsevieren_US
dc.titleOpposing Effects of Glutamine and Asparagine Govern Prion Formation by Intrinsically Disordered Proteinsen_US
dc.typeArticleen_US
dc.identifier.citationHalfmann, Randal, Simon Alberti, Rajaraman Krishnan, Nicholas Lyle, Charles W. O’Donnell, Oliver D. King, Bonnie Berger, Rohit V. Pappu, and Susan Lindquist. “Opposing Effects of Glutamine and Asparagine Govern Prion Formation by Intrinsically Disordered Proteins.” Molecular Cell 43, no. 1 (July 2011): 72–84. © 2011 Elsevier Inc.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratoryen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Electrical Engineering and Computer Scienceen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Mathematicsen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorBerger, Bonnieen_US
dc.contributor.mitauthorO'Donnell, Charles Williamen_US
dc.contributor.mitauthorLindquist, Susanen_US
dc.contributor.mitauthorHalfmann, Randal Arthuren_US
dc.relation.journalMolecular Cellen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsHalfmann, Randal; Alberti, Simon; Krishnan, Rajaraman; Lyle, Nicholas; O'Donnell, Charles W.; King, Oliver D.; Berger, Bonnie; Pappu, Rohit V.; Lindquist, Susanen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-1307-882X
dc.identifier.orcidhttps://orcid.org/0000-0002-2724-7228
dspace.mitauthor.errortrue
mit.licensePUBLISHER_POLICYen_US


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