Structural insights into the transmembrane domains of human copper transporter 1

2012 ◽  
Vol 18 (7) ◽  
pp. 449-455 ◽  
Author(s):  
Lei Yang ◽  
Zhaowei Huang ◽  
Fei Li
Keyword(s):  
Transmembrane Domains ◽  
Copper Transporter ◽  
Copper Transporter 1 ◽  
Structural Insights

scholarly journals Copper Promotes Tumorigenesis by Activating the PDK1‐AKT Oncogenic Pathway in a Copper Transporter 1 Dependent Manner

2021 ◽  
pp. 2004303
Author(s):  
Jianping Guo ◽  
Ji Cheng ◽  
Nana Zheng ◽  
Xiaomei Zhang ◽  
Xiaoming Dai ◽  
...  
Keyword(s):  
Dependent Manner ◽  
Copper Transporter ◽  
Oncogenic Pathway ◽  
Copper Transporter 1

scholarly journals Structural insights into the activation of human calcium-sensing receptor

2021 ◽  
Author(s):  
Xiaochen Chen ◽  
Lu Wang ◽  
Zhanyu Ding ◽  
Qianqian Cui ◽  
Li Han ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Large Scale ◽  
Transmembrane Domains ◽  
Structural Basis ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Cryo Electron Microscopy ◽  
Activation Mechanisms ◽  
G Protein Coupled ◽  
Structural Insights

AbstractHuman calcium-sensing receptor (CaSR) is a G-protein-coupled receptor that maintains Ca2+ homeostasis in serum. Here, we present the cryo-electron microscopy structures of the CaSR in the inactive and active states. Complemented with previously reported crystal structures of CaSR extracellular domains, it suggests that there are three distinct conformations: inactive, intermediate and active state during the activation. We used a negative allosteric nanobody to stabilize the CaSR in the fully inactive state and found a new binding site for Ca2+ ion that acts as a composite agonist with L-amino acid to stabilize the closure of active Venus flytraps. Our data shows that the agonist binding leads to the compaction of the dimer, the proximity of the cysteine-rich domains, the large-scale transitions of 7-transmembrane domains, and the inter-and intrasubunit conformational changes of 7-transmembrane domains to accommodate the downstream transducers. Our results reveal the structural basis for activation mechanisms of the CaSR.

scholarly journals Impact of Expression Levels of Platinum-uptake Transporters Copper Transporter 1 and Organic Cation Transporter 2 on Resistance to Anthracycline/Taxane-based Chemotherapy in Triple-negative Breast Cancer

2015 ◽  
Vol 9 ◽  
pp. BCBCR.S27534
Author(s):  
Risa Takeda ◽  
Ayano Naka ◽  
Naoki Ogane ◽  
Yoichi Kameda ◽  
Kae Kawachi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Platinum Drugs ◽  
Ki 67 ◽  
Copper Transporter ◽  
Organic Cation Transporter 2 ◽  
Uptake Transporters ◽  
Copper Transporter 1

Adding platinum drugs to anthracycline/taxane (ANC-Tax)-based neoadjuvant chemotherapy (NAC) improves pathological complete response (pCR) rates in triple-negative breast cancer (TNBC). Copper transporter 1 (CTR1) and organic cation transporter 2 (OCT2) critically affect the uptake and cytotoxicity of platinum drugs. We immunohistochemically determined CTR1 and OCT2 levels in pre-chemotherapy biopsies from 105 patients with HER2-negative breast cancer treated with ANC-Tax-based NAC. In the TNBC group, Ki-67high [pathological good response (pGR), P = 0.04] was associated with response, whereas CTR1high (non-pGR, P = 0.03), OCT2high (non-pGR, P = 0.01; non-pCR, P = 0.03), and combined CTR1high and/or OCT2high (non-pGR, P = 0.005; non-pCR, P = 0.003) were associated with non-response. In multivariate analysis, Ki-67high was an independent factor for pGR and CTR1 for non-pGR. Combined CTR1/OCT2 was a strong independent factor for non-pGR. However, no variables were associated with response in luminal BC. These results indicate that platinum uptake transporters are predominantly expressed in ANC-Tax-resistant TNBCs, which implies that advantage associated with adding platinum drugs may depend on high drug uptake.

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