Targeting Metastable Coiled-Coil Domains by Computational Design.
Approximately 30% of eukaryotic genomes are predicted to encode partially unfolded proteins. Many of these unstructured domains contact multiple partners in short-lived interactions critical for cellular homeostasis. Understanding the functional implications of these transient binding events is a cu...
| Publicado en: | Journal of the American Chemical Society Vol. 130; no. 36; pp. 12038 - 12045 |
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| Autores principales: | , , |
| Formato: | Artículo |
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American Chemical Society
9/10/2008
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=hlh&AN=34350853&site=ehost-live header: @attributes: shortDbName: hlh uiTerm: 34350853 longDbName: Humanities International Complete uiTag: AN controlInfo: bkinfo: jinfo: jid: 00027863 ACS jtl: Journal of the American Chemical Society issn: 00027863 maglogo: N pubinfo: dt: 9/10/2008 vid: 130 iid: 36 pid: 997 pub: American Chemical Society artinfo: ui: 34350853 10.1021/ja802447e ppf: 12038 ppct: 7 formats: tig: atl: Targeting Metastable Coiled-Coil Domains by Computational Design. aug: au: Barth, Patrick Schoeffler, Allyn Alber, Tom affil: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3220 su: Genomes Proteins Homeostasis Chemical inhibitors Peptides sug: subj: Genomes Proteins Homeostasis Chemical inhibitors Peptides ab: Approximately 30% of eukaryotic genomes are predicted to encode partially unfolded proteins. Many of these unstructured domains contact multiple partners in short-lived interactions critical for cellular homeostasis. Understanding the functional implications of these transient binding events is a current challenge that could be addressed with designed peptide inhibitors. Most current protein design methodologies, however, target only structurally well-defined, stable structures. To address this limitation, we implemented a computational design strategy that alternates between a fixed backbone sequence search for binding specificity and structural optimization of the designed interfaces. We applied this method to create specific peptide inhibitors of the C-terminal metastable coiled-coil domain of the essential yeast septin Cdc12p. Specific binding of the designed sequences was demonstrated by circular dichroism and equilibrium ultracentrifugation. Our results validate computational methods to design specific peptide ligands to protein domains lacking intrinsic structural stability and set the stage for functional analysis of Cdc12p coiled coil function in vivo. pubtype: Academic Journal doctype: Article src: R language: English refInfo: copyright: @attributes: flag: Y dt: @attributes: year: 2008 holdings: @attributes: islocal: N |
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