X-ray structures of the high-affinity copper transporter Ctr1

Abstract

Copper (Cu) is an essential trace element for growth and development and abnormal Cu levels are associated with anemia, metabolic disease and cancer. Evolutionarily conserved from fungi to humans, the high-affinity Cu + transporter Ctr1 is crucial for both dietary Cu uptake and peripheral distribution, yet the mechanisms for selective permeation of potentially toxic Cu + ions across cell membranes are unknown. Here we present X-ray crystal structures of Ctr1 from Salmo salar in both Cu + -free and Cu + -bound states, revealing a homo-trimeric Cu + -selective ion channel-like architecture. Two layers of methionine triads form a selectivity filter, coordinating two bound Cu + ions close to the extracellular entrance. These structures, together with Ctr1 functional characterization, provide a high resolution picture to understand Cu + import across cellular membranes and suggest therapeutic opportunities for intervention in diseases characterized by inappropriate Cu accumulation.

Reconfiguration, Camouflage, and Color‐Shifting for Bioinspired Adaptive Hydrogel‐Based Millirobots

“…Different from ferrite materials, NdFeB microparticles have high remanent magnetization and larger magnetic coercivity, which ensure that the magnetization profile (M) can be maintained during magnetic actuation, thus enabling excellent magnetic actuation of robots. [37][38][39] Moreover, this unique design of magnetization profile solely within the head of iRobot enables greater potential not only to realize high mobility, but also to achieve outstanding functions.…”

Self‐Folding Using Capillary Forces

“…Therefore, droplet selfwrapping necessarily involves stretching as well as bending of the substrate; conversely, continuous substrates can be tailored with cuts to achieve predetermined self-wrapping into 3D spheroidal shapes and thus maximize the ratio of surface to enclosed volume. [78,[89][90][91] Third, downscaling benefits elastocapillary folding, since L EC scales with sheet thickness t to the power of 3/2 and thinner substrates are associated with smaller critical lengths. Hence, 10-100 nm-sized nanostructures can conceivably be self-folded out of atomically thin sheets.…”

Damaging Intermolecular Energy and Proton Transfer Processes in Alpha‐Particle‐Irradiated Hydrogen‐Bonded Systems

“…[9,10] Since ICD may happen between biologically relevant molecules, [11] in biomolecule-water pairs, [12,13] or between two water monomers, [14,15] it contributes to both direct and indirect damaging events.Indeed, through ICD,the initially deposited energy is converted into ap roduction of al ow energy electron and two cationic species [16] among which water cations cause perhaps the biggest concern because of their fast transformation to reactive hydroxyl radicals.I ti sa lso noteworthy that ICD-induced charge separation may lead to bond-breaking Coulomb explosion of energetic fragments. [13,14,17] While most of the existing experiments have been performed using electromagnetic radiation, ICD was also identified after collisions with charged particles such as electrons, [13,[18][19][20] alpha particles, [21][22][23] and heavy ions. [23][24][25] An important distinctive property of collisions with alpha particles is an enhanced production of dicationic states.…”

“…[27] In aw eakly bound atomic cluster,t he common relaxation process of localized low-energy dicationic states is radiative charge transfer (RCT), which brings the system into charge-separated states. [19,20,24,25] In molecular aggregates,slow RCT is usually outperformed by much faster intramolecular fragmentation given that electronic decays are energetically forbidden. In the present study we report on an ew very efficient relaxation mechanism of localized lowenergy dicationic states in molecular systems bound by weak hydrogen bonds that is competitive to the above processes.…”

“…Thesame delocalized dicationic states can also be created through SI of two different molecular centers in the dimer. Like in ICD,s uch double ionization will be followed by Coulomb explosion of the C 2 H 2 + fragments.A lthough ICD and SI can hardly be separated unambiguously,w eb elieve that the latter is only am inor channel here.O ur belief is partially based on the estimates made in the recent electron impact ionization experiments [13,19] indicating that the SI…”