Asymmetric Pendrin Homodimer Reveals its Molecular Mechanism as Anion Exchanger

Pendrin SLC26A4 is an anion exchanger expressed in apical membranes of selected epithelia. Pendrin ablation causes Pendred syndrome, a genetic disorder disease associated with sensorineural hearing loss, hypothyroid goiter, and reduced blood pressure. However, its molecular structure has remained unknown limiting our understanding. Here, we determined the structures of mouse pendrin with symmetric and characteristically asymmetric homodimer conformations by cryo-electron microscopy. The asymmetric homodimer consists of an inward-facing protomer and an intermediate-state protomer, representing the coincident uptake and secretion process, and exhibits the unique state of pendrin as an electroneutral exchanger. This previously unrevealed conformation, together with other conformations we captured, provides an inverted alternate-access mechanism for anion exchange. Furthermore, our structural and functional data disclosed the properties of anion exchange cleft and interpreted the important pathogenetic mutations. These investigations shed light on the pendrin exchange mechanism and extend our structure-guided understanding of pathogenetic mutations.

Increasing the efficiency of rare earth metal recovery from technological solutions during processing of apatite raw materials

The issues of complex processing of mineral resources are relevant due to the depletion of available raw materials. So, it is necessary to involve technological waste, generated during the processing of raw materials, to obtain valuable components. In the process flow of apatite concentrate treatment using the sulfuric acid method, a large amount of phosphogypsum is produced with an average content of light rare earth metals (REMs) reaching 0.032-0.45 %. When phosphogypsum is treated with sulfuric acid solutions, a part of REMs is transferred to the sulfate solution, from which it can be extracted by means of ion exchange method. The study focuses on sorption recovery of light REMs (praseodymium, neodymium and samarium) in the form of anionic sulfate complexes of the composition [ln(SO4)2]– on polystyrene anion exchanger AN-31. The experiments were performed under static conditions at a liquid-to-solid ratio of 1:1, pH value of 2, temperature of 298 K and initial REM concentration in the solutions ranging from 0.83 to 226.31 mmol/kg. Thermodynamic description of sorption isotherms was carried out by the method based on linearization of the mass action equation, modified for the ion exchange reaction. As a result of performed calculations, the authors obtained the constants of ion exchange equilibrium for Pr, Nd and Sm, as well as the values of the change in the Gibbs energy for the ion exchange of REM sulfate complexes on the AN-31 anion exchanger and the values of total capacity of the anion exchanger. Calculated separation factors indicated low selectivity of AN-31 anionite exchanger for light REMs; however, the anion exchanger is suitable for effective recovery of a sum of light REMs. Based on the average value of ion exchange equilibrium constant for light REMs, parameters of a sorption unit with a fluidized bed of anion exchanger were estimated.

SLC4A2 anion exchanger promotes tumour cell malignancy via enhancing net acid efflux across golgi membranes

Proper functioning of each secretory and endocytic compartment relies on its unique pH micro-environment that is known to be dictated by the rates of V-ATPase-mediated H+ pumping and its leakage back to the cytoplasm via an elusive “H+ leak” pathway. Here, we show that this proton leak across Golgi membranes is mediated by the AE2a (SLC4A2a)-mediated bicarbonate-chloride exchange, as it is strictly dependent on bicarbonate import (in exchange for chloride export) and the expression level of the Golgi-localized AE2a anion exchanger. In the acidic Golgi lumen, imported bicarbonate anions and protons then facilitate a common buffering reaction that yields carbon dioxide and water before their egress back to the cytoplasm via diffusion or water channels. The flattened morphology of the Golgi cisternae helps this process, as their high surface-volume ratio is optimal for water and gas exchange. Interestingly, this net acid efflux pathway is often upregulated in cancers and established cancer cell lines, and responsible for their markedly elevated Golgi resting pH and attenuated glycosylation potential. Accordingly, AE2 knockdown in SW-48 colorectal cancer cells was able to restore these two phenomena, and at the same time, reverse their invasive and anchorage-independent growth phenotype. These findings suggest a possibility to return malignant cells to a benign state by restoring Golgi resting pH.