ABC transporters form the largest of all transporter families, and their structural study has made tremendous progress over recent years. However, despite such advances, the precise mechanisms that determine the energy-coupling between ATP hydrolysis and the conformational changes following substrate binding remain to be elucidated. Here, we present our thermodynamic analysis for both ABC importers and exporters, and introduce the two new concepts of differential-binding energy and elastic conformational energy into the discussion. We hope that the structural analysis of ABC transporters will henceforth take thermodynamic aspects of transport mechanisms into account as well.
ATP-Binding Cassette Transporters ; physiology ; Adenosine Triphosphate ; metabolism ; Animals ; Humans ; Models, Theoretical ; Thermodynamics

ATP-binding cassette(ABC) transporters are one of the largest protein families in organisms, with important effects in regulating plant growth and development, root morphology, transportation of secondary metabolites and resistance of stress. Environmental stress promotes the biosynthesis and accumulation of secondary metabolites, which determines the quality of medicinal plants. Therefore, how to improve the accumulation of secondary metabolites has been a hotspot in studying medicinal plants. Many studies have showed that ABC transporters are extremely related to the transportation and accumulation of secondary metabolites in plants. Recently, with the great development of genomics and transcriptomic sequencing technology, the regulatory mechanisms of ABC transporters on secondary metabolites have attached great attentions in medicinal plants. This paper reviewed the mechanisms of different groups of ABC transporters in transporting secondary metabolites through cell membranes. This paper provided key theoretical basis and technical supports in studying the mechanisms of ABC transporters in medicinal plant, and promoting the accumulation of secondary metabolites, in order to improve the quality of medicinal plants.
ATP-Binding Cassette Transporters/metabolism* ; Biological Transport ; Plant Development ; Plants, Medicinal/metabolism* ; Stress, Physiological

To explore the correlation between single nucleotide polymorphisms (SNPs) of hormone receptor gene or other related genes and axillary osmidrosis (AO).
 Methods: Whole blood samples of 219 patients with AO and 159 normal people were collected, and their genomic DNA was extracted. SNPs of 49 selected gene loci were detected and analyzed by using matrix-assisted laser analysis and ionization time of flight mass spectrometry and other related technologies.
 Results: There were significant differences in SNPs at rs1256061 of estrogen receptor β gene and rs17822931, rs16945916 and rs62058521 in ABCC11 gene between the AO patients and normal people (all P<0.01). 81.1% of patients with AO carried G allele at rs1256061, while only 63.2% of normal people carried G allele; 96.3% of patients with AO carried G allele at rs17822931, while only 4.4% of the normal people carried G allele; 28.6% of the patients with armpit odor carried the G allele of rs16945916, while only 0.6% of the normal people carried G allele; 28.0% of patients with AO carried G allele at rs62058521, while only 0.6% of the normal people carried G allele.
 Conclusion: SNPs of rs1256061 at the locus of estrogen receptor gene are correlated with the pathogenesis of AO, while SNPs at multiple loci (rs16945916, rs62058521 and rs17822931) in ABCC11 gene are correlated with the pathogenesis of AO.
ATP-Binding Cassette Transporters ; genetics ; Axilla ; Estrogen Receptor beta ; genetics ; Genotype ; Humans ; Polymorphism, Single Nucleotide

ATP-Binding Cassette Transporters/genetics* ; Follow-Up Studies ; Humans ; Infant ; Lung ; Lung Diseases, Interstitial/genetics*

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.
Siderophores/metabolism* ; Iron/metabolism* ; Mycobacterium tuberculosis/metabolism* ; Cryoelectron Microscopy ; Adenosine Triphosphate/metabolism* ; ATP-Binding Cassette Transporters

Aromatic compounds are a class of organic compounds with benzene ring(s). Aromatic compounds are hardly decomposed due to its stable structure and can be accumulated in the food cycle, posing a great threat to the ecological environment and human health. Bacteria have a strong catabolic ability to degrade various refractory organic contaminants (e.g., polycyclic aromatic hydrocarbons, PAHs). The adsorption and transportation are prerequisites for the catabolism of aromatic compounds by bacteria. While remarkable progress has been made in understanding the metabolism of aromatic compounds in bacterial degraders, the systems responsible for the uptake and transport of aromatic compounds are poorly understood. Here we summarize the effect of cell-surface hydrophobicity, biofilm formation, and bacterial chemotaxis on the bacterial adsorption of aromatic compounds. Besides, the effects of outer membrane transport systems (such as FadL family, TonB-dependent receptors, and OmpW family), and inner membrane transport systems (such as major facilitator superfamily (MFS) transporter and ATP-binding cassette (ABC) transporter) involved in the membrane transport of these compounds are summarized. Moreover, the mechanism of transmembrane transport is also discussed. This review may serve as a reference for the prevention and remediation of aromatic pollutants.
Humans ; Adsorption ; Bacteria/metabolism* ; Organic Chemicals ; Biological Transport ; ATP-Binding Cassette Transporters ; Polycyclic Aromatic Hydrocarbons/metabolism*

Sterols are a class of cyclopentano-perhydrophenanthrene derivatives widely present in living organisms. Sterols are important components of cell membranes. In addition, they also have important physiological and pharmacological activities. With the development of synthetic biology and metabolic engineering technology, yeast cells are increasingly used for the heterologous synthesis of sterols in recent years. Nevertheless, since sterols are hydrophobic macromolecules, they tend to accumulate in the membrane fraction of yeast cells and consequently trigger cytotoxicity, which hampers the further improvement of sterols yield. Therefore, revealing the mechanism of sterol transport in yeast, especially understanding the working principle of sterol transporters, is vital for designing strategies to relieve the toxicity of sterol accumulation and increasing sterol yield in yeast cell factories. In yeast, sterols are mainly transported through protein-mediated non-vesicular transport mechanisms. This review summarizes five types of sterol transport-related proteins that have been reported in yeast, namely OSBP/ORPs family proteins, LAM family proteins, ABC transport family proteins, CAP superfamily proteins, and NPC-like sterol transport proteins. These transporters play important roles in intracellular sterol gradient distribution and homeostasis maintenance. In addition, we also review the current status of practical applications of sterol transport proteins in yeast cell factories.
Saccharomyces cerevisiae/genetics* ; Sterols ; Phytosterols ; Biological Transport ; ATP-Binding Cassette Transporters/genetics*

OBJECTIVETo identify the mutational genotype of three Chinese families with X-linked adrenoleukodystrophy (X-ALD: MIM#300100).

METHODSTotal RNA was extracted from the peripheral blood leukocytes of patients 1, 2 and the mother of patient 3, using RNA blood Mini kit (QIAGEN). After reverse transcription, cDNA was amplified in four overlapping segments. The PCR products were purified and directly sequenced. To confirm the mutations, the genomic DNA was isolated from the patients and their family members using DNA blood isolation kit (MO-BIO) and analyzed by PCR-restrictive digestion or amplification refractory mutation system.

RESULTSThree distinct mutations were detected in the ABCD1 gene of the three pedigrees. A mutation of CCC-->CGC was detected at codon 534 of the ABCD1 gene from patient 1, resulting in the arginine for proline substitution. A change of GGG-->AGG was found at codon 266 of the second patient's gene, accompanied with the replacement of glycine by arginine. A mutation of CGC-->GGC was found at codon 617 in one ABCD1 allele of the third patient's mother, leading to the glycine for arginine substitution. The three mutations were confirmed through restriction analysis or amplification refractory mutation system.

CONCLUSIONThree ABCD1 gene missense mutations were detected in three unrelated Chinese families with X-linked adrenoleukodystrophy, one of which, the mutation (P534R), is novel in Chinese with ALD, and the other two G266R and R617G mutations, have been reported outside China.

ATP Binding Cassette Transporter, Sub-Family D, Member 1 ; ATP-Binding Cassette Transporters ; genetics ; Adrenoleukodystrophy ; genetics ; Child ; Child, Preschool ; Humans ; Male ; Mutation ; Pedigree

OBJECTIVETo investigate the potential role of anthocyanins on modulating cholesterol efflux in mouse peritoneal macrophage-derived foam cells and related molecular mechanisms.

METHODSThe macrophages were isolated from pathogen-free NIH mice and were loaded with 50 microg/ml oxLDL for 24 hours, newly formed foam cells were then treated with anthocyanins (cyanidin-3-glucoside, Cy-3-g; or peonidin-3-glucoside, Pn-3-g) at the concentrations of 1 micromol/L, 10 micromol/L, 100 micromol/L for 0 to 36 hours, respectively. The enzymatic-fluorescent method was used to determine cholesterol content in culture medium. ABCA1 expressions at mRNA and protein level were detected by real-time PCR and confocal microscope.

RESULTSCholesterol efflux of macrophage-derived foam cells increased in a time- and dose-dependent manner post anthocyanins treatment. ABCA1 expressions at mRNA and protein levels were also significantly enhanced after anthocyanins treatment in these cells and these effects could be blocked by co-treatment with DIDS, an inhibitor of the transport activities of ABCA1 and blocker of apoAI-mediated cholesterol efflux.

CONCLUSIONThese data demonstrate that anthocyanins induce cholesterol efflux from mouse peritoneal macrophage-derived foam cells via regulating ABCA1 expression.

ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters ; metabolism ; Animals ; Anthocyanins ; pharmacology ; Cells, Cultured ; Cholesterol ; metabolism ; Foam Cells ; drug effects ; metabolism ; Macrophages, Peritoneal ; cytology ; Mice

OBJECTIVETo investigate the effect of 5-fluorouracil (5-FU) on the expression of ATP-binding cassette superfamily G member 2 (ABCG2) in human colon cancer cell SW480.

METHODSSW480 cells were treated with various concentrations of 5-FU. CCK8 assay was utilized to detect the 5-FU IC50 to SW480 cells. Positive expression of ABCG2 was detected by flow cytometry, and mRNA expression of ABCG2 was detected by real time polymerase chain reaction (RT-PCR).

RESULTSThe 5-FU IC50 to SW480 cells increased as the drug concentration increased (P<0.05). Flow cytometry revealed that positive expression rate of ABCG2 in normal SW480 cells (group A) was (6.26±0.86)%. Immediately after treatment with 5-FU for 48 hours, the positive expression rate of ABCG2 (group B) was (3.43±1.18)% (P<0.05). In the second passage of cells after treatment with 5-FU for 48 hours, the positive expression rate of ABCG2 (group C) was (12.91±3.42)% (P<0.05). The mRNA expression of ABCG2 detected by RT-PCR was in accordance with the results from flow cytometry.

CONCLUSIONExpression of ABCG2 in SW480 cells can be affected by various concentrations of 5-FU.

ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; Cell Line, Tumor ; Colonic Neoplasms ; metabolism ; Fluorouracil ; pharmacology ; Humans ; Neoplasm Proteins ; metabolism