Abstract:
:The proton-coupled folate transporter (PCFT, SLC46A1) transports folic acid across the plasma membrane, together with an excess of protons such that the net charge translocation is positive. We developed 3D structural models of PCFT threaded onto the X-ray structures of major facilitator superfamily (MFS) members that were identified as close structural homologues. The model of PCFT threaded onto the glycerol-3-phosphate transporter (GlpT) structure is consistent with detailed accessibility studies in the absence of extracellular substrate and at pH 7.4 presented here, and additionally with a multitude of other mutagenesis and functional studies. Characteristic MFS structural features are preserved in this PCFT model, such as 12 transmembrane helices divided into two pseudosymmetric bundles, and a high density of positive charges on the periphery of the cytoplasmic site that allow interactions with negatively charged lipid head-groups. Under the experimental conditions, PCFT predominantly samples the resting state, which in this case is inward-open. Several positions lining the substrate cavity have been identified. Motif A, a helix-turn-helix motif that is a hallmark of MFS transporters between transmembrane segments II and III is oriented appropriately to interact with residues from transmembrane segments IV as well as XI upon conformational transition to the outward-open state. A charge-relay system between three charged residues as well as apposing glycines in two α-helices, both contributed to by motif A, become engaged when PCFT is modeled on the outward-open state of a putative proton-driven transporter (YajR).
journal_name
FEBS Open Biojournal_title
FEBS open bioauthors
Date SS,Chen CY,Chen Y,Jansen Mdoi
10.1002/2211-5463.12041subject
Has Abstractpub_date
2016-02-22 00:00:00pages
216-30issue
3issn
2211-5463pii
FEB412041journal_volume
6pub_type
杂志文章相关文献
FEBS Open Bio文献大全abstract::Ki-67 (MKI67) is a marker of cellular proliferation of cancer. Here, we show that Ki-67 is post-transcriptionally regulated through alternative polyadenylation (APA) and microRNAs in breast cancer. We show that shortening of the Ki-67 3'UTR results in the loss of the binding sites for the suppressive miRNAs and thus r...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12364
更新日期:2018-01-26 00:00:00
abstract::Receptor activator of nuclear factor-κB ligand (RANKL) is required for initiation of osteoclastogenesis, with the signaling pathway including the NF-kB, c-Fos, and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) transcription factors. Because NFATc1 expression is autoamplified, we investigated the molecula...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12513
更新日期:2018-09-10 00:00:00
abstract::Colorectal cancer (CRC) is the third main cause of cancer-relevant deaths worldwide, and its incidence has increased in recent decades. Previous studies have indicated that certain long non-coding RNAs (lncRNAs) have regulatory roles in tumor occurrence and progression. Often, lncRNAs are competitive endogenous RNAs (...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12802
更新日期:2020-01-27 00:00:00
abstract::The extreme halophile Halococcus morrhuae (ATCC® 17082) contains a 108-nucleotide insertion in its 5S rRNA. Large rRNA expansions in Archaea are rare. This one almost doubles the length of the 5S rRNA. In order to understand how such an insertion is accommodated in the ribosome, we obtained a cryo-electron microscopy ...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12962
更新日期:2020-10-01 00:00:00
abstract::Niclosamide is a potent inhibitor of osteoclastogenesis and bone remodeling. DK-520 is an acyl derivative of Niclosamide and significantly increased both the plasma concentration and the duration of exposure of Niclosamide when dosed orally. However, at present the effect of DK-520 on osteoclastogenesis has not been r...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12921
更新日期:2020-08-01 00:00:00
abstract::The identification of biomarkers for early diagnosis of Parkinson's disease (PD) prior to the onset of symptoms may improve the effectiveness of therapy. To identify potential biomarkers, we downloaded microarray datasets of PD from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between PD...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12687
更新日期:2019-08-01 00:00:00
abstract::Neural stem cells (NSC) from the adult hippocampus easily lose their activity in vitro. Efficient in vitro expansion of adult hippocampus-derived NSC is important for generation of tools for research and cell therapy. Here, we show that a single copy disruption or pharmacological inhibition of p38α enables successful ...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2015.05.001
更新日期:2015-05-08 00:00:00
abstract::Flavin adenine dinucleotide (FAD), synthesized from riboflavin, is redox cofactor in energy production and plays an important role in cell survival. More recently, riboflavin deficiency has been linked to developmental disorders, but its role in stem cell differentiation remains unclear. Here, we show that FAD treatme...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12331
更新日期:2017-10-17 00:00:00
abstract::An imbalance of branched-chain amino acids (BCAAs) in the brain may result in neuropathological conditions, such as autism spectrum disorders. The L-type amino acid transporter 1 (LAT1), encoded by the solute carrier transporter 7a5 (Slc7a5) gene, is critical for maintaining normal levels of BCAAs in the brain. Howeve...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12559
更新日期:2019-01-07 00:00:00
abstract::A great number of studies have proven that sHsps protect cells by inhibiting protein aggregation under heat stress, while little is known about their function to protect cells under acid stress. In this work, we show that Hsp20.1 and Hsp14.1 oligomers dissociated to smaller oligomeric species or even dimer/monomer at ...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2015.02.006
更新日期:2015-03-05 00:00:00
abstract::Adult T-cell leukemia/lymphoma (ATL), an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukemia virus (HTLV-1), requires new treatments. Drug repositioning, reuse of a drug previously approved for the treatment of another condition to treat ATL, offers the possibility of reduce...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12055
更新日期:2016-04-13 00:00:00
abstract::Osteonecrosis of the femoral head (ONFH) is a common clinical disease with a high disability rate. Apoptosis of osteoblasts caused by high-dose short-term or low-dose long-term glucocorticoid (GC) administration is the biological basis of steroid-induced avascular necrosis of the femoral head (SANFH). The pathogenesis...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.13037
更新日期:2020-11-15 00:00:00
abstract::l-Ornithine cyclodeaminase (OCD) is involved in l-proline biosynthesis and catalyzes the unique deaminating cyclization of l-ornithine to l-proline via a Δ(1)-pyrroline-2-carboxyrate (Pyr2C) intermediate. Although this pathway functions in only a few bacteria, many archaea possess OCD-like genes (proteins), among whic...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2014.07.005
更新日期:2014-07-10 00:00:00
abstract::Sorafenib is an inhibitor of a variety of tyrosine kinase receptors used to treat various cancers including hepatocellular, renal cell and thyroid carcinoma. It has been shown to change various targets associated with osteosarcoma, but the detailed mechanism remains unclear. In order to identify key genes, enriched pa...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12428
更新日期:2018-04-24 00:00:00
abstract::The major functions of adipocytes include both lipid storage and the production of secretory factors. However, the type of proteins released from mouse 3T3-L1 cells during adipocyte differentiation remains poorly understood. We examined the dynamics of secreted proteins during adipocyte differentiation using mass spec...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12091
更新日期:2016-06-15 00:00:00
abstract::Inorganic polyphosphate (polyP) is a linear polymer containing tens to hundreds of orthophosphate residues linked by high-energy phosphoanhydride bonds. PolyP promotes osteocalcification and bone mineralization in both mouse and human osteoblastic cells. In the present study, we examined the molecular mechanism by whi...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12703
更新日期:2019-09-01 00:00:00
abstract::NrrF is a small regulatory RNA of the human pathogen Neisseria meningitidis. NrrF was previously shown to repress succinate dehydrogenase (sdhCDAB) under control of the ferric uptake regulator (Fur). Here, we provide evidence that cytochrome bc 1 , encoded by the polycistro...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12266
更新日期:2017-08-05 00:00:00
abstract::Glioma is one of the most common types of malignant primary central nervous system tumor, and prognosis for this disease is poor. As autophagic drugs have been reported to induce glioma cell death, we investigated the potential prognostic role of autophagy-associated long non-coding RNA (lncRNA) in glioma patients. In...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12601
更新日期:2019-03-05 00:00:00
abstract::Soft cheese with white rind lacks essential fatty acids (EFAs), and as a result its long-term consumption may lead to various kinds of cardiovascular and cerebrovascular diseases, such as hyperlipidemia, hypertension, and atherosclerosis. Geotrichum candidum is a dimorphic yeast that plays an important role in the rip...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12553
更新日期:2018-12-06 00:00:00
abstract::Angiotensin converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase with an essential role in blood pressure homeostasis in mammals. ACE has long been targeted in the treatment of hypertension through ACE inhibitors, however current inhibitors are known to cause severe side effects. Therefore, there is...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2015.08.004
更新日期:2015-08-11 00:00:00
abstract::The bacterial phosphotransferase system is central to sugar uptake and phosphorylation. Enzyme I (EI), the first enzyme of the system, autophosphorylates as a dimer using phosphoenolpyruvate (PEP), but it is not clearly understood how dimerization activates the enzyme activity. Here, we show that EI dimerization is im...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12260
更新日期:2017-07-17 00:00:00
abstract::The gene encoding MG Orn has been identified from a metagenomic library created from the intertidal zone in Svalbard and encodes a protein of 184 amino acid residues. The mg orn gene has been cloned, recombinantly expressed in Escherichia coli, and purified to homogeneity. Biochemical characterization of the enzyme sh...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12720
更新日期:2019-10-01 00:00:00
abstract::A plant-derived Enterococcus mundtii 15-1A, that has been previously isolated from Brassica rapa L. subsp. nipposinica (L.H. Bailey) Hanelt var. linearifolia by our group, possesses two kinds of l-lactate dehydrogenase (l-LDH): LDH-1 and LDH-2. LDH-1 was activated under low concentration of fluctose-1,6-bisphosphate (...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2014.08.006
更新日期:2014-09-06 00:00:00
abstract::Flavonoids represent one of the most important molecules of plant secondary metabolism, playing many different biochemical and physiological roles. Although their essential role in plant life and human health has been elucidated by many studies, their subcellular transport and accumulation in plant tissues remains unc...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2015.08.009
更新日期:2015-08-29 00:00:00
abstract::Synthetic biology circuits are often constructed with multiple gene expression units assembled in close proximity, and they can be used to perform complex functions in embryonic stem cells (ESCs). However, mutual interference between transcriptional units has not been well studied in mouse ESCs. To assess the efficien...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12818
更新日期:2020-04-01 00:00:00
abstract::Goji berries have been used as food and medicine for millennia. Due to their high morphological similarity, fruits of two distinct species belonging to the family Solanaceae, Lycium barbarum (LB) and Lycium chinense (Chinese boxthorn), are usually marketed together as goji berries, but nearly 90% of all commercially a...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12910
更新日期:2020-08-01 00:00:00
abstract::The base excision repair pathway plays an important role in correcting damage induced by either physiological or external effects. This repair pathway removes incorrect bases from the DNA. The uracil base is among the most frequently occurring erroneous bases in DNA, and is cut out from the phosphodiester backbone via...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12567
更新日期:2019-02-09 00:00:00
abstract::Osteosarcoma is a malignant bone tumor, and clinically detectable metastases can be detected in ~ 15-20% of patients when they seek medical advice; patients with metastatic disease have extremely poor prognosis. Here, we examined the involvement of the microRNA miR-505 in osteosarcoma. Eighty-four patients seeking tre...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12868
更新日期:2020-07-01 00:00:00
abstract::Osteoarthritis (OA) is a chronic degenerative disease that commonly affects the elderly. Current drug therapies for treating OA may cause adverse side effects, and so there remains a need to develop alternative treatments. Bergapten (BG) is a coumarin phytohormone that is widely found in fruits and has antioxidative a...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1002/2211-5463.12648
更新日期:2019-06-01 00:00:00
abstract::Transformation of fungi by complementation of auxotrophs is generally much more reliable than usage of antibiotic resistance markers. In order to establish such a system for the model zygomycete Absidia glauca, a stable methionine auxotrophic mutant was isolated after X-ray mutagenesis of the minus mating type and cha...
journal_title:FEBS open bio
pub_type: 杂志文章
doi:10.1016/j.fob.2012.07.002
更新日期:2012-07-20 00:00:00