Molecular insight into coordination sites for substrates and their coupling kinetics in Na⁺/HCO₃⁻ cotransporter NBCe1

Abstract

support-information-section).

Who's on first … Na+, HCO3− or CO32−?

“…This initial Na + binding provides favourable protein energetics in the form of a favourable chemical gradient and often an accompanying protein conformational change to accommodate or bind the other ions or solutes. Figure 4F and G from Wu et al (2022) shows that decreasing [HCO 3 − ] results in an increased apparent K m for Na + while changing [Na + ] has no obvious effect of the K m for HCO 3 − for either NBCe1-A or NBCe1-B. Additionally, the modelling and mutation experiments reveal that the more distal spaces allow the more selective coordination by the proximal immediate side-chains, for example F840A on I803A and I803A on T436S (Fig.…”

“…Specifically, when Na + and HCO 3 − move from the outside world to the intracellular world, the anion sites accommodate the trigonal planar HCO 3 − . Nevertheless, when ions move out of the cell, one of these same anion sites accommodates the also trigonal planar CO 3 2− (Figs 9,10, 13 from Wu et al., 2022).…”

“…Additionally, the modelling and mutation experiments reveal that the more distal spaces allow the more selective coordination by the proximal immediate side-chains, for example F840A on I803A and I803A on T436S (Fig. 8, Wu et al, 2022).…”

“…That said, why apparently different coordination occurs in an efflux mode and why this 'change' does not seem to occur at both anion sites, is not known. The paper by Wu et al (2022) emphasizes the importance of repeating experiments, especially when new tools, for example molecular structures, are available. Interestingly, the modelling experiments indicate that the NBCe1 structure can also accommodate two CO 3 2− ions indicating that 3-net negative charges could be moved through NBCe1.…”

“…The current paper (Wu et al., 2022) tests the human NBCe1‐A and ‐B isoforms using varying [Na + ], [HCO 3 − ], [CO 3 2− ] and membrane voltage ( V m or V clamp ) while probing the cryo‐EM structure‐predicted binding sites (Huynh et al., 2018). This is the first study to probe the ionic coupling of NBCe1‐B as well as NBCe1‐A.…”