dc.contributor.authorKang, CongBao
dc.contributor.authorBharatham, Nagakumar
dc.contributor.authorChia, Joel
dc.contributor.authorMu, Yuguang
dc.contributor.authorBaek, Kwanghee
dc.contributor.authorYoon, Ho Sup
dc.date.accessioned2013-07-03T03:01:15Z
dc.date.available2013-07-03T03:01:15Z
dc.date.copyright2012en_US
dc.date.issued2012
dc.identifier.citationKang, C., Bharatham, N., Chia, J., Mu, Y., Baek, K., & Yoon, H. S. (2012). The Natively Disordered Loop of Bcl-2 Undergoes Phosphorylation-Dependent Conformational Change and Interacts with Pin1. PLoS ONE, 7(12), e52047.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10220/10901
dc.description.abstractBcl-2 plays a central role in the regulation of apoptosis. Structural studies of Bcl-2 revealed the presence of a flexible and natively disordered loop that bridges the Bcl-2 homology motifs, BH3 and BH4. This loop is phosphorylated on multiple sites in response to a variety of external stimuli, including the microtubule-targeting drugs, paclitaxel and colchicine. Currently, the underlying molecular mechanism of Bcl-2 phosphorylation and its biological significance remain elusive. In this study, we investigated the molecular characteristics of this anti-apoptotic protein. To this end, we generated synthetic peptides derived from the Bcl-2 loop, and multiple Bcl-2 loop truncation mutants that include the phosphorylation sites. Our results demonstrate that S87 in the flexible loop of Bcl-2 is the primary phosphorylation site for JNK and ERK2, suggesting some sequence or structural specificity for the phosphorylation by these kinases. Our NMR studies and molecular dynamics simulation studies support indicate that phosphorylation of S87 induces a conformational change in the peptide. Finally, we show that the phosphorylated peptides of the Bcl-2 loop can bind Pin1, further substantiating the phosphorylation-mediated conformation change of Bcl-2.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesPLoS ONEen_US
dc.rights© 2012 The Authors. This paper was published in PLoS ONE and is made available as an electronic reprint (preprint) with permission of The Authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1371/journal.pone.0052047 ]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.en_US
dc.subjectDRNTU::Science::Biological sciences
dc.titleThe natively disordered loop of Bcl-2 undergoes phosphorylation-dependent conformational change and interacts with Pin1en_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0052047
dc.description.versionPublished versionen_US


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