CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Feb. 26, 2018

Abstract Na + -coupled acid–base transporters play essential roles in human biology. Their dysfunction has been linked to cancer, heart, and brain disease. High-resolution structures of mammalian are not available. The sodium-bicarbonate cotransporter NBCe1 functions multiple organs its mutations cause blindness, abnormal growth blood chemistry, migraines, impaired cognitive function. Here, we have determined the structure membrane domain dimer at 3.9 Å resolution by cryo electron microscopy. Our atomic model functional mutagenesis revealed ion accessibility pathway coordination site, latter containing residues involved disease-causing mutations. We identified a small number within site whose modification transformed into an anion exchanger. data suggest that symporters exchangers utilize comparable transport machinery subtle differences their substrate-binding regions very significant effects on mode.

Language: Английский

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Role of Carbonic Anhydrases and Inhibitors in Acid–Base Physiology: Insights from Mathematical Modeling

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(15), P. 3841 - 3841

Published: Aug. 6, 2019

Carbonic anhydrases (CAs) catalyze a reaction fundamental for life: the bidirectional conversion of carbon dioxide (CO2) and water (H2O) into bicarbonate (HCO3-) protons (H+). These enzymes impact numerous physiological processes that occur within across many compartments in body. Within compartments, CAs promote rapid H+ buffering thus stability pH-sensitive processes. Between movements H+, CO2, HCO3-, related species. This traffic is central to respiration, digestion, whole-body/cellular pH regulation. Here, we focus on role mathematical modeling understanding how CA enhances as well gradients drive fluxes CO2 other solutes (facilitated diffusion). We also examine urinary acid secretion carriage by respiratory system. propose broad stem from three actions: promoting buffering, enhancing exchange between buffer systems, facilitating diffusion. Mathematical can be powerful tool for: (1) clarifying complex interdependencies among reaction, diffusion, protein-mediated components processes; (2) formulating hypotheses making predictions tested wet-lab experiments; (3) inferring data are impossible measure.

Language: Английский

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The physiology and genetics of CO2 concentrating mechanisms in model diatoms

Current Opinion in Plant Biology, Journal Year: 2016, Volume and Issue: 31, P. 51 - 57

Published: April 4, 2016

Language: Английский

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Boron: an essential element for vascular plants

New Phytologist, Journal Year: 2019, Volume and Issue: 226(5), P. 1232 - 1237

Published: Nov. 1, 2019

See also the Commentary on this article by McGrath, 226 : 1225–1227 .

Language: Английский

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Acid-base physiology and CO2 homeostasis: Regulation and compensation in response to elevated environmental CO2

Fish physiology, Journal Year: 2019, Volume and Issue: unknown, P. 69 - 132

Published: Jan. 1, 2019

Language: Английский

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