Novel Peptide-Mediated Interactions Derived from High-Resolution 3-Dimensional Structures 英文参考文献.docVIP
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Novel Peptide-Mediated Interactions Derived from High-Resolution 3-Dimensional Structures 英文参考文献
NovelPeptide-MediatedInteractionsDerivedfromHigh-
Resolution3-DimensionalStructures
AmelieStein1,PatrickAloy1,2*
1InstituteforResearchinBiomedicine,JointIRB-BSCPrograminComputationalBiology,Barcelona,Spain,2Institucio′ CatalanadeRecercaiEstudisAvanc?ats,Barcelona,
Spain
Abstract
Manybiologicalresponsestointra-andextracellularstimuliareregulatedthroughcomplexnetworksoftransientprotein
interactionswhereaglobulardomaininoneproteinrecognizesalinearpeptidefromanother,creatingarelativelysmall
contact interface. These peptide stretches are often found in unstructured regions of proteins, and contain a consensus
motifcomplementarytotheinteractionsurfacedisplayedbytheirbindingpartners.Whilemostcurrentmethodsforthede
novo discovery of such motifs exploit their tendency to occur in disordered regions, our work here focuses on another
observation:uponbindingtotheirpartnerdomain,motifsadoptawell-definedstructure.Indeed,throughtheanalysisofall
peptide-mediatedinteractionsofknownhigh-resolutionthree-dimensional(3D)structure,wefoundthatthestructureof
thepeptidemaybeascharacteristicastheconsensusmotif,andhelpidentifytargetpeptideseventhoughtheydonot
match the established patterns. Our analyses of the structural features of known motifs reveal that they tend to have a
particular stretched and elongated structure, unlike most other peptides of the same length. Accordingly, we have
implementedastrategybasedonaSupportVectorMachinethatusesthisfeatures,alongwithotherstructure-encoded
information about binding interfaces, to search the set of protein interactions of known 3D structure and to identify
unnoticed peptide-mediated interactions among them. We have also derived consensus patterns for these interactions,
whenever enough information was available, and compared our results with established linear motif patterns and their
bindingdomains.Finally,tocross-validateouridentificationstrategy,wescannedinteractomenetworksfromfourmodel
organismswithournewlyderivedpatternstoseeifanyof
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