Repozitorij Univerze v Novi Gorici

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Naslov:Dynamical interplay between the human high-affinity copper transporter hCtr1 and its cognate metal ion
Avtorji:ID Walke , Gulshan, Department of Chemistry and the Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat-Gan, Israel. (Avtor)
ID Aupič, Jana, Department National Research Council of Italy (CNR) - Institute of Material (IOM) c/o International School for Advanced Studies (SISSA), Trieste, Italy. (Avtor)
ID Kashoua , Hadeel, Department of Chemistry and the Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat-Gan, Israel. (Avtor)
ID Janoš, Pavel, Department National Research Council of Italy (CNR) - Institute of Material (IOM) c/o International School for Advanced Studies (SISSA), Trieste, Italy. (Avtor)
ID Meron , Shelly, Department of Chemistry and the Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat-Gan, Israel. (Avtor)
ID Shenberger , Yulia, Department of Chemistry and the Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat-Gan, Israel. (Avtor)
ID Qasem , Zena, Department of Chemistry and the Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat-Gan, Israel. (Avtor)
ID Gevorkyan-Airapetov , Lada, Department of Chemistry and the Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat-Gan, Israel. (Avtor)
ID Magistrato, Alessandra, Department National Research Council of Italy (CNR) - Institute of Material (IOM) c/o International School for Advanced Studies (SISSA), Trieste, Italy. (Avtor)
ID Ruthstein , Sharon, Department of Chemistry and the Institute of Nanotechnology and Advanced Materials (BINA), Bar-Ilan University, Ramat-Gan, Israel. (Avtor)
Datoteke: Gradivo nima datotek, ki so prostodostopne za javnost. Gradivo je morda fizično dosegljivo v knjižnici fakultete, zalogo lahko preverite v COBISS-u. Povezava se odpre v novem oknu
Jezik:Angleški jezik
Vrsta gradiva:Delo ni kategorizirano
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:UNG - Univerza v Novi Gorici
Opis:Abnormal cellular copper levels have been clearly implicated in genetic diseases, cancer, and neurodegeneration. Ctr1, a high-affinity copper transporter, is a homotrimeric integral membrane protein that provides the main route for cellular copper uptake. Together with a sophisticated copper transport system, Ctr1 regulates Cu(I) metabolism in eukaryotes. Despite its pivotal role in normal cell function, the molecular mechanism of copper uptake and transport via Ctr1 remains elusive. In this study, electron paramagnetic resonance (EPR), UV-visible spectroscopy, and all-atom simulations were employed to explore Cu(I) binding to full-length human Ctr1 (hCtr1), thereby elucidating how metal binding at multiple distinct sites affects the hCtr1 conformational dynamics. We demonstrate that each hCtr1 monomer binds up to five Cu(I) ions and that progressive Cu(I) binding triggers a marked structural rearrangement in the hCtr1 C-terminal region. The observed Cu(I)-induced conformational remodeling suggests that the C-terminal region may play a dual role, serving both as a channel gate and as a shuttle mediating the delivery of copper ions from the extracellular hCtr1 selectivity filter to intracellular metallochaperones. Our findings thus contribute to a more complete understanding of the mechanism of hCtr1-mediated Cu(I) uptake and provide a conceptual basis for developing mechanism-based therapeutics for treating pathological conditions linked to de-regulated copper metabolism.
Ključne besede:ctr1, copper, epr, molecular dynamics
Leto izida:2022
Št. strani:1194-1204
Številčenje:7, 121
PID:20.500.12556/RUNG-7603 Novo okno
COBISS.SI-ID:121423875 Novo okno
DOI:https://doi.org/10.1016/j.bpj.2022.02.033 Novo okno
NUK URN:URN:SI:UNG:REP:TP1T68P9
Datum objave v RUNG:15.09.2022
Število ogledov:1866
Število prenosov:0
Metapodatki:XML DC-XML DC-RDF
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Gradivo je del revije

Naslov:Biophysical Journal
Leto izida:2022

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