| 1. |
- Avdic, Anders, 1950-, et al.
(författare)
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Development of a Real-time Formative Feedback Student Response System
- 2014
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Ingår i: Journal of Network and Innovative Computing. - 2160-2174. ; 2:1, s. 259-268
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Tidskriftsartikel (refereegranskat)abstract
- This paper is focusing IT-supported real-time formative feedback in a classroom context. The development of a Student and Teacher Response System (STRS) is described. Since there are a number of obstacles for effective interaction in large classes, IT can be used to support the teachers aim to find out if students understand the lecture and accordingly adjust the content and design of the lecture. The system can be used for formative assessment before, during, and after a lecture. It is also possible for students to initiate interaction during lectures by posing questions anonymously. The main contributions of the paper are a) the description of the interactive real-time system and b) the development process behind it.
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| 2. |
- Avdic, Anders, et al.
(författare)
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Student and teacher response system : development of an interactive anonymous real-timeformative feedback system
- 2013
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Ingår i: Proceedings of the 2013 Third World Congress on Information and Communication Technologies (WICT 2013). - : IEEE. - 9781479932306 ; , s. 25-30
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Konferensbidrag (refereegranskat)abstract
- This paper is focusing IT-supported real-time formative feedback in a classroom context. The development of a Student and Teacher Response System (STRS) is described. Since there are a number of obstacles for effective interaction in large classes IT can be used to support the teachers aim to find out if students understand the lecture and accordingly adjust the content and design of the lecture. The system can be used for formative assessment before, during, and after a lecture. It is also possible for students to initiate interaction during lectures by posing questions anonymously. The main contributions of the paper are a) the description of the interactive real-time system and b) the development process behind it.
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| 3. |
- Grønberg, Christina, et al.
(författare)
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Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport
- 2016
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Ingår i: Biophysical Journal. - : Elsevier. - 0006-3495 .- 1542-0086. ; 111:11, s. 2417-2429
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Tidskriftsartikel (refereegranskat)abstract
- Cu+-specific P-type ATPase membrane protein transporters regulate cellular copper levels. The lack of crystal structures in Cu+-binding states has limited our understanding of how ion entry and binding are achieved. Here, we characterize the molecular basis of Cu+ entry using molecular-dynamics simulations, structural modeling, and in vitro and in vivo functional assays. Protein structural rearrangements resulting in the exposure of positive charges to bulk solvent rather than to lipid phosphates indicate a direct molecular role of the putative docking platform in Cu+ delivery. Mutational analyses and simulations in the presence and absence of Cu+ predict that the ion-entry path involves two ion-binding sites: one transient Met148-Cys382 site and one intramembranous site formed by trigonal coordination to Cys384, Asn689, and Met717. The results reconcile earlier biochemical and x-ray absorption data and provide a molecular understanding of ion entry in Cu+-transporting P-type ATPases.
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| 4. |
- Grønberg, Christina, et al.
(författare)
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Structure and ion-release mechanism of P IB-4-type ATPases
- 2022
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X.
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Transition metals, such as zinc, are essential micronutrients in all organisms, but alsohighly toxic in excessive amounts. Heavy-metal transporting P-type (PIB) ATPases are crucial forhomeostasis, conferring cellular detoxification and redistribution through transport of these ionsacross cellular membranes. No structural information is available for the PIB-4-ATPases, the subclasswith the broadest cargo scope, and hence even their topology remains elusive. Here, we presentstructures and complementary functional analyses of an archetypal PIB-4-ATPase, sCoaT fromSulfitobacter sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy-metal-binding domains (HMBDs), and provide fundamentally new insights into the mechanism anddiversity of heavy-metal transporters. We reveal several novel P-type ATPase features, includinga dual role in heavy-metal release and as an internal counter ion of an invariant histidine. We alsoestablish that the turnover of PIB-ATPases is potassium independent, contrasting to many otherP-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in forexample drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.
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| 5. |
- Guo, Zongxin, et al.
(författare)
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Diverse roles of the metal binding domains and transport mechanism of copper transporting P-type ATPases
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Copper transporting P-type (P1B-1-) ATPases are essential for cellular homeostasis. Nonetheless, the E1-E1P-E2P-E2 states mechanism of P1B-1-ATPases remains poorly understood. In particular, the role of the intrinsic metal binding domains (MBDs) is enigmatic. Here, four cryo-EM structures and molecular dynamics simulations of a P1B-1-ATPase are combined to reveal that in many eukaryotes the MBD immediately prior to the ATPase core, MBD−1, serves a structural role, remodeling the ion-uptake region. In contrast, the MBD prior to MBD−1, MBD−2, likely assists in copper delivery to the ATPase core. Invariant Tyr, Asn and Ser residues in the transmembrane domain assist in positioning sulfur-providing copper-binding amino acids, allowing for copper uptake, binding and release. As such, our findings unify previously conflicting data on the transport and regulation of P1B-1-ATPases. The results are critical for a fundamental understanding of cellular copper homeostasis and for comprehension of the molecular bases of P1B-1-disorders and ongoing clinical trials.
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| 6. |
- Li, Ping, et al.
(författare)
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Structure and transport mechanism of P5B-ATPases
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- In human cells, P5B-ATPases execute the active export of physiologically important polyamines such as spermine from lysosomes to the cytosol, a function linked to a palette of disorders. Yet, the overall shape of P5B-ATPases and the mechanisms of polyamine recognition, uptake and transport remain elusive. Here we describe a series of cryo-electron microscopy structures of a yeast homolog of human ATP13A2-5, Ypk9, determined at resolutions reaching 3.4 Å, and depicting three separate transport cycle intermediates, including spermine-bound conformations. Surprisingly, in the absence of cargo, Ypk9 rests in a phosphorylated conformation auto-inhibited by the N-terminus. Spermine uptake is accomplished through an electronegative cleft lined by transmembrane segments 2, 4 and 6. Despite the dramatically different nature of the transported cargo, these findings pinpoint shared principles of transport and regulation among the evolutionary related P4-, P5A- and P5B-ATPases. The data also provide a framework for analysis of associated maladies, such as Parkinson’s disease.
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| 7. |
- Salustros, Nina, et al.
(författare)
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Structural basis of ion uptake in copper-transporting P1B-type ATPases
- 2022
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Copper is essential for living cells, yet toxic at elevated concentrations. Class 1B P-type (P1B-) ATPases are present in all kingdoms of life, facilitating cellular export of transition metals including copper. P-type ATPases follow an alternating access mechanism, with inward-facing E1 and outward-facing E2 conformations. Nevertheless, no structural information on E1 states is available for P1B-ATPases, hampering mechanistic understanding. Here, we present structures that reach 2.7 Å resolution of a copper-specific P1B-ATPase in an E1 conformation, with complementing data and analyses. Our efforts reveal a domain arrangement that generates space for interaction with ion donating chaperones, and suggest a direct Cu+ transfer to the transmembrane core. A methionine serves a key role by assisting the release of the chaperone-bound ion and forming a cargo entry site together with the cysteines of the CPC signature motif. Collectively, the findings provide insights into P1B-mediated transport, likely applicable also to human P1B-members.
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| 8. |
- Wiuf, Anders, et al.
(författare)
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The two-domain elevator-type mechanism of zinc-transporting ZIP proteins
- 2022
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Ingår i: Science Advances. - : American Association for the Advancement of Science. - 2375-2548. ; 8:28
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Tidskriftsartikel (refereegranskat)abstract
- Zinc is essential for all organisms and yet detrimental at elevated levels. Hence, homeostasis of this metal is tightly regulated. The Zrt/Irt-like proteins (ZIPs) represent the only zinc importers in metazoans. Mutations in human ZIPs cause serious disorders, but the mechanism by which ZIPs transfer zinc remains elusive. Hitherto, structural information is only available for a model member, BbZIP, and as a single, ion-bound conformation, precluding mechanistic insights. Here, we elucidate an inward-open metal-free BbZIP structure, differing substantially in the relative positions of the two separate domains of ZIPs. With accompanying coevolutional analyses, mutagenesis, and uptake assays, the data point to an elevator-type transport mechanism, likely shared within the ZIP family, unifying earlier functional data. Moreover, the structure reveals a previously unknown ninth transmembrane segment that is important for activity in vivo. Our findings outline the mechanistic principles governing ZIP-protein transport and enhance the molecular understanding of ZIP-related disorders.
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