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Intrinsic disorder mediates cooperative signal transduction in STIM1

Furukawa, Yukio; Teraguchi, Shunsuke; Ikegami, Takahisa; Dagliyan, Onur; Jin, Lin; Hall, Damien; Dokholyan, Nikolay V.; Namba, Keiichi; Akira, Shizuo; Kurosaki, Tomohiro; Baba, Yoshihiro; Standley, Daron M.

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Intrinsically disordered domains have been reported to play important roles in signal transduction networks by introducing cooperativity into protein-protein interactions. Unlike intrinsically disordered domains that become ordered upon binding, the EF-SAM domain in the stromal interaction molecule (STIM) 1 is distinct in that it is ordered in the monomeric state and partially unfolded in its oligomeric state, with the population of the two states depending on the local Ca2 + concentration. The...[Show more]

dc.contributor.authorFurukawa, Yukio
dc.contributor.authorTeraguchi, Shunsuke
dc.contributor.authorIkegami, Takahisa
dc.contributor.authorDagliyan, Onur
dc.contributor.authorJin, Lin
dc.contributor.authorHall, Damien
dc.contributor.authorDokholyan, Nikolay V.
dc.contributor.authorNamba, Keiichi
dc.contributor.authorAkira, Shizuo
dc.contributor.authorKurosaki, Tomohiro
dc.contributor.authorBaba, Yoshihiro
dc.contributor.authorStandley, Daron M.
dc.date.accessioned2015-12-10T23:08:03Z
dc.identifier.issn0022-2836
dc.identifier.urihttp://hdl.handle.net/1885/63131
dc.description.abstractIntrinsically disordered domains have been reported to play important roles in signal transduction networks by introducing cooperativity into protein-protein interactions. Unlike intrinsically disordered domains that become ordered upon binding, the EF-SAM domain in the stromal interaction molecule (STIM) 1 is distinct in that it is ordered in the monomeric state and partially unfolded in its oligomeric state, with the population of the two states depending on the local Ca2 + concentration. The oligomerization of STIM1, which triggers extracellular Ca2 + influx, exhibits cooperativity with respect to the local endoplasmic reticulum Ca 2 + concentration. Although the physiological importance of the oligomerization reaction is well established, the mechanism of the observed cooperativity is not known. Here, we examine the response of the STIM1 EF-SAM domain to changes in Ca2 + concentration using mathematical modeling based on in vitro experiments. We find that the EF-SAM domain partially unfolds and dimerizes cooperatively with respect to Ca2 + concentration, with Hill coefficients and half-maximal activation concentrations very close to the values observed in vivo for STIM1 redistribution and extracellular Ca 2 + influx. Our mathematical model of the dimerization reaction agrees quantitatively with our analytical ultracentrifugation-based measurements and previously published free energies of unfolding. A simple interpretation of these results is that Ca2 + loss effectively acts as a denaturant, enabling cooperative dimerization and robust signal transduction. We present a structural model of the Ca2 +-unbound EF-SAM domain that is consistent with a wide range of evidence, including resistance to proteolytic cleavage of the putative dimerization portion.
dc.publisherElsevier
dc.sourceJournal of Molecular Biology
dc.titleIntrinsic disorder mediates cooperative signal transduction in STIM1
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume426
dc.date.issued2014
local.identifier.absfor030406 - Proteins and Peptides
local.identifier.absfor030403 - Characterisation of Biological Macromolecules
local.identifier.ariespublicationu4005981xPUB773
local.type.statusPublished Version
local.contributor.affiliationFurukawa, Yukio, Osaka University
local.contributor.affiliationTeraguchi, Shunsuke, Osaka University
local.contributor.affiliationIkegami, Takahisa, Osaka University
local.contributor.affiliationDagliyan, Onur, University of North Carolina at Chapel Hill
local.contributor.affiliationJin, Lin, Osaka University
local.contributor.affiliationHall, Damien, College of Physical and Mathematical Sciences, ANU
local.contributor.affiliationDokholyan, Nikolay V., University of North Carolina at Chapel Hill
local.contributor.affiliationNamba, Keiichi, Osaka University
local.contributor.affiliationAkira, Shizuo, Osaka University
local.contributor.affiliationKurosaki, Tomohiro, Osaka University
local.contributor.affiliationBaba, Yoshihiro, Osaka University
local.contributor.affiliationStandley, Daron M., Osaka University
local.description.embargo2037-12-31
local.bibliographicCitation.issue10
local.bibliographicCitation.startpage2082
local.bibliographicCitation.lastpage2097
local.identifier.doi10.1016/j.jmb.2014.03.006
local.identifier.absseo970106 - Expanding Knowledge in the Biological Sciences
local.identifier.absseo970103 - Expanding Knowledge in the Chemical Sciences
dc.date.updated2015-12-10T09:04:25Z
local.identifier.scopusID2-s2.0-84899638075
local.identifier.thomsonID000336349000006
CollectionsANU Research Publications

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