Fig. 6: Schematic representation of alternating access transport in KimA.
From: Structural basis of proton-coupled potassium transport in the KUP family
The outward-open conformation should provide access of protons and potassium ions from the extracellular side to the binding sites, while at the cytoplasmic side the exit tunnel should be tightly sealed. The binding of a proton and a potassium ion could result in the movement of Y43, which serves as external gate occluding the bound substrate. Subsequently, broken helices TM1 and TM6 could alternate, sealing the extracellular tunnel and opening the intracellular tunnel. A thin, intracellular gate formed by residues D36 and Y377 could yet sustain an occluded state. Upon deprotonation of E233, the intracellular gate could open, allowing potassium ion release to the cytoplasm. At high intracellular potassium concentrations, potassium ions could bind within the intracellular tunnel preventing the opening of the intracellular gate. We hypothesize that our cryo-EM structure represents such a trans-inhibited, inward-occluded state (highlighted with dashed box).
