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dc.contributor.authorTossavainen, Helena
dc.contributor.authorAitio, Olli
dc.contributor.authorHellman, Maarit
dc.contributor.authorSaksela, Kalle
dc.contributor.authorPermi, Perttu
dc.date.accessioned2016-08-22T10:40:39Z
dc.date.available2017-06-06T21:45:07Z
dc.date.issued2016
dc.identifier.citationTossavainen, H., Aitio, O., Hellman, M., Saksela, K., & Permi, P. (2016). Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2. <i>Journal of Biological Chemistry</i>, <i>291</i>(31), 16307-16317. <a href="https://doi.org/10.1074/jbc.M116.732412" target="_blank">https://doi.org/10.1074/jbc.M116.732412</a>
dc.identifier.otherCONVID_26171956
dc.identifier.otherTUTKAID_70947
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/50988
dc.description.abstractWe show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728–1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nM). Our NMR solution complex structure together with isothermal titration calorimetry data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure, indicating that a transient or fluctuating polyelectrostatic interaction accounts for this affinity. Thus, via optimization of such dynamic electrostatic forces, viral peptides have evolved a superior binding affinity for amphiphysin-2 SH3 compared with typical cellular ligands, such as dynamin, thereby enabling hijacking of amphiphysin-2 SH3-regulated host cell processes by these viruses. Moreover, our data show that the previously described consensus sequence PXRPXR for amphiphysin SH3 ligands is inaccurate and instead define it as an extended Class II binding motif PXXPXRpXR, where additional positive charges between the two constant arginine residues can give rise to extraordinary high SH3 binding affinity.
dc.language.isoeng
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc.
dc.relation.ispartofseriesJournal of Biological Chemistry
dc.subject.otherChikungunya virus
dc.subject.otherdynamin
dc.subject.otherhost-pathogen interaction
dc.subject.otherintrinsically disordered protein
dc.subject.othernuclear magnetic resonance (NMR)
dc.subject.otherprotein structure
dc.subject.otherSrc homology 3 domain (SH3 domain)
dc.subject.otheramphiphysin SH3
dc.subject.othernsP3
dc.titleStructural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201608183821
dc.contributor.laitosBio- ja ympäristötieteiden laitosfi
dc.contributor.laitosKemian laitosfi
dc.contributor.laitosDepartment of Biological and Environmental Scienceen
dc.contributor.laitosDepartment of Chemistryen
dc.contributor.oppiaineSolu- ja molekyylibiologiafi
dc.contributor.oppiaineOrgaaninen kemiafi
dc.contributor.oppiaineNanoscience Centerfi
dc.contributor.oppiaineCell and Molecular Biologyen
dc.contributor.oppiaineOrganic Chemistryen
dc.contributor.oppiaineNanoscience Centeren
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.date.updated2016-08-18T12:15:03Z
dc.type.coarjournal article
dc.description.reviewstatuspeerReviewed
dc.format.pagerange16307-16317
dc.relation.issn0021-9258
dc.relation.numberinseries31
dc.relation.volume291
dc.type.versionpublishedVersion
dc.rights.copyright© 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Published in this repository with the kind permission of the publisher.
dc.rights.accesslevelopenAccessfi
dc.relation.doi10.1074/jbc.M116.732412


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