| 11. |
- Lazar, Tamas, et al.
(författare)
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PED in 2021 : A major update of the protein ensemble database for intrinsically disordered proteins
- 2021
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 49:D1, s. 404-411
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Tidskriftsartikel (refereegranskat)abstract
- The Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. The new version, PED 4.0, has been completely redesigned and reimplemented with cutting-edge technology and now holds about six times more data (162 versus 24 entries and 242 versus 60 structural ensembles) and a broader representation of state of the art ensemble generation methods than the previous version. The database has a completely renewed graphical interface with an interactive feature viewer for region-based annotations, and provides a series of descriptors of the qualitative and quantitative properties of the ensembles. High quality of the data is guaranteed by a new submission process, which combines both automatic and manual evaluation steps. A team of biocurators integrate structured metadata describing the ensemble generation methodology, experimental constraints and conditions. A new search engine allows the user to build advanced queries and search all entry fields including cross-references to IDP-related resources such as DisProt, MobiDB, BMRB and SASBDB. We expect that the renewed PED will be useful for researchers interested in the atomic-level understanding of IDP function, and promote the rational, structure-based design of IDP-targeting drugs.
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| 12. |
- Möller, Per, et al.
(författare)
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Severnaya Zemlya, Arctic Russia: a nucleation area for Kara Sea ice sheets during the Middle to Late Quaternary
- 2006
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 25:21-22, s. 2894-2936
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Tidskriftsartikel (refereegranskat)abstract
- Quaternary glacial stratigraphy and relative sea-level changes reveal at least four expansions of the Kara Sea ice sheet over the Severnaya Zemlya Archipelago at 79 degrees N in the Russian Arctic, as indicated from tills interbedded with marine sediments, exposed in stratigraphic superposition, and from raised-beach sequences that occur at altitudes up to 140 m a.s.l. Chronologic control is provided by AMS C-14, electron-spin resonance, green-stimulated luminescence, and aspartic-acid geochronology. Major glaciations followed by deglaciation and marine inundation occurred during MIS 10-9, MIS 8-7, MIS 6-5e and MIS 5d-3. The MIS 6-5e event, associated with the high marine limit, implies ice-sheet thickness of > 2000m only 200km from the deep Arctic Ocean, consistent with published evidence of ice grounding at similar to 1000m water depth in the central Arctic Ocean. Till fabrics and glacial tectonics record repeated expansions of local ice caps exclusively, suggesting wet-based ice cap advance followed by cold-based regional ice-sheet expansion. Local ice caps over highland sites along the perimeter of the shallow Kara Sea, including the Byrranga Mountains, appear to have repeatedly fostered initiation of a large Kara Sea ice sheet, with exception of the Last Glacial Maximum (MIS 2), when Kara Sea ice did not impact Severnaya Zemlya and barely graced northernmost Taymyr Peninsula.
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| 13. |
- Ahlner, Alexandra, 1984-, et al.
(författare)
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Conformational Dynamics and Multimerization of Active Forms of the EphrinB Receptor 2 Kinase Domain
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Active and autoinhibited forms of the ephrinB receptor 2 (EphB2) kinase domain have been studied using NMR spectroscopy. The project was initiated because of the finding that the crystal structures of active forms of the kinase domain and previous NMR studies suggested that a change in inter-lobe flexibility and the sampling of catalytically competent excited states conformations are responsible for activity. Using Carr-Purcell-Meiboom-Gill relaxation dispersion experiments, we have measured millisecond dynamics to identify such states. We have also performed concentration dependent relaxation experiments and analytical ultracentrifugation experiments that report on the effective protein size to look for possible differences in self-association for active and autoinhibited forms of the EphB2 kinase domain. We show that the active but not autoinhibited forms exchange between a ground state and an excited state at a rate of 1900 s-1. Similar results were found for the S677/680A mutant of the protein. The nature and importance of the excited state is still unknown. Our most important finding is that active forms of the kinase domain self-associate in a concentration dependent manner and form tetramers and possibly larger oligomers. Multimerization of the kinase domain may enable the assembly of complexes of downstream proteins and could be important for Eph signaling.
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| 14. |
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| 15. |
- Andrésen, Cecilia, et al.
(författare)
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Transient structure and dynamics in the disordered c-Myc transactivation domain affect Bin1 binding
- 2012
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP): Policy C / Oxford University Press. - 0305-1048 .- 1362-4962. ; 40:13, s. 6353-6366
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Tidskriftsartikel (refereegranskat)abstract
- The crucial role of Myc as an oncoprotein and as a key regulator of cell growth makes it essential to understand the molecular basis of Myc function. The N-terminal region of c-Myc coordinates a wealth of protein interactions involved in transformation, differentiation and apoptosis. We have characterized in detail the intrinsically disordered properties of Myc-1-88, where hierarchical phosphorylation of S62 and T58 regulates activation and destruction of the Myc protein. By nuclear magnetic resonance (NMR) chemical shift analysis, relaxation measurements and NOE analysis, we show that although Myc occupies a very heterogeneous conformational space, we find transiently structured regions in residues 22-33 and in the Myc homology box I (MBI; residues 45-65); both these regions are conserved in other members of the Myc family. Binding of Bin1 to Myc-1-88 as assayed by NMR and surface plasmon resonance (SPR) revealed primary binding to the S62 region in a dynamically disordered and multivalent complex, accompanied by population shifts leading to altered intramolecular conformational dynamics. These findings expand the increasingly recognized concept of intrinsically disordered regions mediating transient interactions to Myc, a key transcriptional regulator of major medical importance, and have important implications for further understanding its multifaceted role in gene regulation.
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| 16. |
- Andrésen, Cecilia, et al.
(författare)
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Transient structure and intrinsic disorder in the c-Myc transactivation domain and its effects on ligand binding
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The crucial role of c-Myc as an oncoprotein and as a key regulator of cell growth makes it essential to understand the molecular basis of c-Myc function. The transactivation domain of c-Myc coordinates a wealth of protein interactions involved in transformation, differentiation and apoptosis. We have characterized in detail the intrinsically disordered properties of c-Myc-1-88, where hierarchical phosphorylation of T58 and S62 regulates activation and destruction of the c-Myc protein. By NMR chemical shift analysis, relaxation measurements and NOE analysis, we show that both the MBI region (residues 45-65) and residues 22-33 are transiently structured regions, conserved also in other members of the Myc family. Binding of Bin1-SH3 to c-Myc-1-88 as assayed by NMR and SPR revealed primary binding to the S62 region, but also a dynamically disordered and multivalent complex in which intrinsic disorder of c-Myc-1-88 was retained while releasing transient intramolecular interactions. Our findings describe a novel mode of regulatory recognition of c-Myc that is in agreement with the increasingly recognized capability of intrinsically disordered regions to efficiently mediate transient interactions with a wide range of targets, with important implications towards understanding the unique multifaceted biological functions of c-Myc.
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