dc.contributor.author | Penkler, David | |
dc.contributor.author | Şensoy, Özge | |
dc.contributor.author | Atılgan, Canan | |
dc.contributor.author | Taştan Bishop, Özlem | |
dc.date.accessioned | 10.07.201910:49:13 | |
dc.date.accessioned | 2019-07-10T19:57:35Z | |
dc.date.available | 10.07.201910:49:13 | |
dc.date.available | 2019-07-10T19:57:35Z | |
dc.date.issued | 2017 | en_US |
dc.identifier.citation | Penkler, D., Şensoy, Ö., Atılgan, C. ve Bishop Taştan, Ö. (2017). Perturbation-response scanning reveals key residues for allosteric control in Hsp70. Journal of Chemical Information and Modeling, 57(6), 1359-1374. https://dx.doi.org/10.1021/acs.jcim.6b00775 | en_US |
dc.identifier.issn | 1549-9596 | |
dc.identifier.issn | 1549-960X | |
dc.identifier.uri | https://dx.doi.org/10.1021/acs.jcim.6b00775 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12511/3008 | |
dc.description | WOS: 000404422600013 | en_US |
dc.description | PubMed ID: 28505454 | en_US |
dc.description.abstract | Hsp70 molecular chaperones play-an important role in maintaining-cellular homeostasis, and are implicated in a wide array of cellular processes, including protein recovery from aggregates, cross-membrane protein translocation, and protein biogenesis. Hsp70 consists of two domains, a nucleotide binding domain (NBD) and a substrate binding domain (SBD), each of which communicates via an allosteric mechanism such that the protein interconverts between two functional states,- an ATP-bound open: conformation and an ADP-bound Closed "conformation, The exact mechanism for interstate conversion is not as yet fully understood. However, the ligand-bound states of the NBD and SBD as well as interactions with cochaperones such as DnaJ and nucleOtide exchange factor are thought to play crucial regulatory roles. In this study, we apply the perturbation response scanning (PRS) method in combination with molecular dynamics simulations as a computational, tool for the identification of allosteric hot residues in the large multidomain Hsp70 protein. We find evidence in support of the hypothesis that substrate binding triggers ATP hydrolysis and that the ADP substrate complex favors interstate conversion to the closed state. Purthenriore, our data are in agreement with the proposal that there is an allosterically active intermediate state between the open and closed states and vice versa, as we find evidence that ATP binding to the closed structure and peptide binding to the open structure allosterically "activate" the respective complexes. We conclude our analysis' y showing how our PRS data fit the current opinion on the Hsp70 conformational cycle and present several allosteric hot residues that may provide a platform for further studies to gain additional insight into Hsp70 allostery. | en_US |
dc.description.sponsorship | National Institutes of Health [U41HG006941]; National Research Foundation (NRF), South Africa [93690]; Scientific and Technological Research Council of Turkey [110T624] | en_US |
dc.description.sponsorship | The authors thank the Centre for High Performance Computing (CHPC), South Africa, for computing time. This work was partially supported by the National Institutes of Health Common Fund under Grant U41HG006941 to H3ABioNet; the National Research Foundation (NRF), South Africa (Grant 93690), and the Scientific and Technological Research Council of Turkey (Grant 110T624). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the funders. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | American Chemical Society | en_US |
dc.rights | info:eu-repo/semantics/embargoedAccess | en_US |
dc.subject | Hsp70 | en_US |
dc.subject | Allosteric Control | en_US |
dc.subject | Key Residues | en_US |
dc.title | Perturbation-response scanning reveals key residues for allosteric control in Hsp70 | en_US |
dc.type | article | en_US |
dc.relation.ispartof | Journal of Chemical Information and Modeling | en_US |
dc.department | İstanbul Medipol Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Bilgisayar Mühendisliği Bölümü | en_US |
dc.authorid | 0000-0001-5950-3436 | en_US |
dc.identifier.volume | 57 | en_US |
dc.identifier.issue | 6 | en_US |
dc.identifier.startpage | 1359 | en_US |
dc.identifier.endpage | 1374 | en_US |
dc.relation.ec | info:eu-repo/grantAgreement/TUBITAK/SOBAG/110T624 | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.identifier.doi | 10.1021/acs.jcim.6b00775 | en_US |
dc.identifier.wosquality | Q1 | en_US |
dc.identifier.scopusquality | Q1 | en_US |