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The structural pathway of interleukin 1 (IL-1) initiated signaling reveals mechanisms of oncogenic mutations and SNPs in inflammation and cancer

dc.contributor.coauthorNussinov, Ruth
dc.contributor.departmentDepartment of Computer Engineering
dc.contributor.departmentGraduate School of Sciences and Engineering
dc.contributor.departmentDepartment of Chemical and Biological Engineering
dc.contributor.departmentCCBB (The Center for Computational Biology and Bioinformatics)
dc.contributor.kuauthorGürsoy, Attila
dc.contributor.kuauthorKeskin, Özlem
dc.contributor.kuauthorÖzbabacan, Saliha Ece Acuner
dc.contributor.schoolcollegeinstituteCollege of Engineering
dc.contributor.schoolcollegeinstituteResearch Center
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF SCIENCES AND ENGINEERING
dc.date.accessioned2024-11-09T11:55:41Z
dc.date.issued2014
dc.description.abstractStructural pathways are important because they provide insight into signaling mechanisms; help understand the mechanism of disease-related mutations; and help in drug discovery. While extremely useful, common pathway diagrams lacking structural data are unable to provide mechanistic insight to explain oncogenic mutations or SNPs. Here we focus on the construction of the IL-1 structural pathway and map oncogenic mutations and SNPs to complexes in this pathway. Our results indicate that computational modeling of protein-protein interactions on a large scale can provide accurate, structural atom-level detail of signaling pathways in the human cell and help delineate the mechanism through which a mutation leads to disease. We show that the mutations either thwart the interactions, activating the proteins even in their absence or stabilize them, leading to the same uncontrolled outcome. Computational mapping of mutations on the interface of the predicted complexes may constitute an effective strategy to explain the mechanisms of mutations- constitutive activation or deactivation.
dc.description.fulltextYES
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue2
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuTÜBİTAK
dc.description.sponsorshipNational Cancer Institute, National Institutes of Health
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TÜBİTAK) Fellowship
dc.description.versionPublisher version
dc.description.volume10
dc.identifier.doi10.1371/journal.pcbi.1003470
dc.identifier.eissn1553-7358
dc.identifier.embargoNO
dc.identifier.filenameinventorynoIR00153
dc.identifier.issn1553-734X
dc.identifier.quartileQ1
dc.identifier.scopus2-s2.0-84895765208
dc.identifier.urihttps://hdl.handle.net/20.500.14288/831
dc.identifier.wos332016700031
dc.keywordsMathematical and computational biology
dc.keywordsSomatic mutations
dc.keywordsMolecular docking
dc.keywordsBrain-tumors
dc.keywordsData-bank
dc.keywordsReceptor
dc.keywordsKinase
dc.keywordsScale
dc.keywordsExpression
dc.keywordsInterfaces
dc.language.isoeng
dc.publisherPublic Library of Science
dc.relation.grantnoHHSN261200800001E
dc.relation.grantno113E164
dc.relation.ispartofPLOS Computational Biology
dc.relation.urihttp://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/1183
dc.subjectBiochemical research methods
dc.subjectBiochemistry and molecular biology
dc.titleThe structural pathway of interleukin 1 (IL-1) initiated signaling reveals mechanisms of oncogenic mutations and SNPs in inflammation and cancer
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorGürsoy, Attila
local.contributor.kuauthorÖzbabacan, Saliha Ece Acuner
local.contributor.kuauthorKeskin, Özlem
local.publication.orgunit1College of Engineering
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