Effect of Intracellular Loop 3 on Intrinsic Dynamics of Human 2-Adrenergic Receptor
dc.authorid | Akten, Ebru Demet/0000-0002-0358-3171 | |
dc.authorid | Doruker, Pemra/0000-0002-4824-2223 | |
dc.authorwosid | Akten, Ebru Demet/AAG-7752-2019 | |
dc.contributor.author | Ozcan, Ozer | |
dc.contributor.author | Uyar, Arzu | |
dc.contributor.author | Doruker, Pemra | |
dc.contributor.author | Akten, Ebru Demet | |
dc.date.accessioned | 2023-10-19T15:11:34Z | |
dc.date.available | 2023-10-19T15:11:34Z | |
dc.date.issued | 2013 | |
dc.department-temp | [Ozcan, Ozer] Bogazici Univ, Computat Sci & Engn Program, Istanbul, Turkey; [Ozcan, Ozer; Uyar, Arzu; Doruker, Pemra] Bogazici Univ, Polymer Res Ctr, Istanbul, Turkey; [Uyar, Arzu; Doruker, Pemra] Bogazici Univ, Dept Chem Engn, Istanbul, Turkey; [Akten, Ebru Demet] Kadir Has Univ, Fac Nat Sci & Engn, Dept Bioinformat & Genet, TR-34083 Istanbul, Turkey | en_US |
dc.description.abstract | Background: To understand the effect of the long intracellular loop 3 (ICL3) on the intrinsic dynamics of human beta(2)-adrenergic receptor, molecular dynamics (MD) simulations were performed on two different models, both of which were based on the inactive crystal structure in complex with carazolol (after removal of carazolol and T4-lysozyme). In the so-called loop model, the ICL3 region that is missing in available crystal structures was modeled as an unstructured loop of 32-residues length, whereas in the clipped model, the two open ends were covalently bonded to each other. The latter model without ICL3 was taken as a reference, which has also been commonly used in recent computational studies. Each model was embedded into POPC bilayer membrane with explicit water and subjected to a 1 mu s molecular dynamics (MD) simulation at 310 K. Results: After around 600 ns, the loop model started a transition to a very inactive conformation, which is characterized by a further movement of the intracellular half of transmembrane helix 6 (TM6) towards the receptor core, and a close packing of ICL3 underneath the membrane completely blocking the G-protein's binding site. Concurrently, the binding site at the extracellular part of the receptor expanded slightly with the Ser207-Asp113 distance increasing to 18 angstrom from 11 angstrom, which was further elaborated by docking studies. Conclusions: The essential dynamics analysis indicated a strong coupling between the extracellular and intracellular parts of the intact receptor, implicating a functional relevance for allosteric regulation. In contrast, no such transition to the very inactive state, nor any structural correlation, was observed in the clipped model without ICL3. Furthermore, elastic network analysis using different conformers for the loop model indicated a consistent picture on the specific ICL3 conformational change being driven by global modes. | en_US |
dc.description.sponsorship | Scientific and Technological Research Council of Turkey (TUBITAK) [109 M281]; State Planning Organization of Turkey (DPT) [2009 K120520]; Kadir Has University BAP [2010-BAP-04]; Bogazici University BAP Project [5714] | en_US |
dc.description.sponsorship | This work has been partially supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project # 109 M281), State Planning Organization of Turkey (DPT) (Project # 2009 K120520) and Kadir Has University BAP (Project # 2010-BAP-04). PD acknowledges partial support by Bogazici University BAP Project (No:5714). | en_US |
dc.identifier.citation | 28 | |
dc.identifier.doi | 10.1186/1472-6807-13-29 | en_US |
dc.identifier.issn | 1472-6807 | |
dc.identifier.issn | 1472-6807 | |
dc.identifier.pmid | 24206668 | en_US |
dc.identifier.scopus | 2-s2.0-84887031430 | en_US |
dc.identifier.uri | https://doi.org/10.1186/1472-6807-13-29 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12469/5096 | |
dc.identifier.volume | 13 | en_US |
dc.identifier.wos | WOS:000329232300002 | en_US |
dc.institutionauthor | Akdoğan, Ebru Demet | |
dc.khas | 20231019-WoS | en_US |
dc.language.iso | en | en_US |
dc.publisher | Bmc | en_US |
dc.relation.ispartof | Bmc Structural Biology | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | Protein-Coupled Receptor | |
dc.subject | Beta(2) Adrenergic-Receptor | |
dc.subject | Human Beta-2-Adrenergic Receptor | |
dc.subject | Molecular-Dynamics | |
dc.subject | Protein-Coupled Receptor | En_Us |
dc.subject | Crystal-Structure | |
dc.subject | Beta(2) Adrenergic-Receptor | En_Us |
dc.subject | Human Beta-2-Adrenergic Receptor | En_Us |
dc.subject | Binding-Site | |
dc.subject | Molecular-Dynamics | En_Us |
dc.subject | Cytoplasmic Domains | |
dc.subject | Crystal-Structure | En_Us |
dc.subject | Binding-Site | En_Us |
dc.subject | Partial Agonists | |
dc.subject | Cytoplasmic Domains | En_Us |
dc.subject | Model | |
dc.subject | ICL3 | en_US |
dc.subject | Partial Agonists | En_Us |
dc.subject | Molecular dynamics simulation | en_US |
dc.subject | Transmembrane helix 6 | en_US |
dc.subject | Model | En_Us |
dc.subject | G-protein binding site | en_US |
dc.subject | Activation | |
dc.subject | Ligand docking | en_US |
dc.subject | Activation | En_Us |
dc.subject | Essential dynamics | en_US |
dc.title | Effect of Intracellular Loop 3 on Intrinsic Dynamics of Human 2-Adrenergic Receptor | en_US |
dc.type | Article | en_US |
dspace.entity.type | Publication | |
relation.isAuthorOfPublication | 558d2b8e-c713-49e0-9350-d354abb5cd69 | |
relation.isAuthorOfPublication.latestForDiscovery | 558d2b8e-c713-49e0-9350-d354abb5cd69 |
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