Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structure of NHE6 and its lipid-mediated interactions regulating endosomal pH.
Journal, issue, pages	Nat Commun, Vol. 17, Issue 1, Year 2026
Publish date	Aug 11, 2026
Authors	Sukkyeong Jung / Hyunku Yeo / Hang Li / Surabhi Kokane / Tom Reichenbach / Ashutosh Gulati / Giuseppe Albano / Carla Kirschbaum / Tin Manh Ho / Michael Landreh / Mia Abramsson / Carol V Robinson / Daniel G Fuster / David Drew /
PubMed Abstract	Sodium-proton exchangers (NHEs) are found in all cells to regulate intracellular pH, sodium levels and cell volume. In humans, there are nine different NHE transporters (SLC9A1-9), which vary in ...Sodium-proton exchangers (NHEs) are found in all cells to regulate intracellular pH, sodium levels and cell volume. In humans, there are nine different NHE transporters (SLC9A1-9), which vary in tissue distribution, kinetics and regulation. NHE6 localizes to endosomal membranes and mutations in the protein are known to cause the X-linked neurological disorder Christianson syndrome. Despite its importance, the structural basis of NHE6 function and regulation is unclear. Here we report four cryo-electron microscopy structures of rat NHE6 between 2.2 and 3.3 Å resolution, revealing its homodimeric structure, ion binding and remodelling by lipids. We characterize a lipid-binding site between the protomers that accommodates the endosomal-specific phosphatidylinositol 3-phosphate (PI3P) lipid. Using solid-supported membrane (SSM)-based electrophysiology we demonstrate that NHE6 transports both Na and K ions and that PI3P enhances NHE6 stability and activity. Furthermore, we identify a phosphatidylinositol 4,5-bisphosphate (PI(4,5)P) lipid, which interacts with the C-terminal domain of NHE6 to stabilize an auto-inhibited state. We further demonstrate that NHE6 is non-functional when mislocalized to the plasma membrane where PI(4,5)P is primarily located. We propose the lipid-dependent regulation has evolved to shut-down NHE6 activity during recycling of endosomes at the plasma membrane.
External links	Nat Commun / PubMed:42581050 / PubMed Central
Methods	EM (single particle)
Resolution	2.28 - 3.25 Å
Structure data	54659 9s8c EMDB-54659, PDB-9s8c: Cryo-EM structure of Rat NHE6 D293A variant Method: EM (single particle) / Resolution: 2.28 Å 54660 9s8d EMDB-54660, PDB-9s8d: Cryo-EM structure of Rat NHE6 in detergent Method: EM (single particle) / Resolution: 2.74 Å 54661 9s8e EMDB-54661, PDB-9s8e: Cryo-EM structure of Rat NHE6 in nanodisc Method: EM (single particle) / Resolution: 3.25 Å 54662 9s8g EMDB-54662, PDB-9s8g: Cryo-EM structure of Rat NHE6 K351A variant Method: EM (single particle) / Resolution: 2.38 Å
Chemicals	PDB-1jmm: Crystal structure of the V-region of Streptococcus mutans antigen I/II ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipidYM ChemComp-PEE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, phospholipidYM ChemComp-PIO: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate ChemComp-LPP: 2-(HEXADECANOYLOXY)-1-[(PHOSPHONOOXY)METHYL]ETHYL HEXADECANOATE / phospholipidYM ChemComp-NA: Unknown entry ChemComp-PLC: DIUNDECYL PHOSPHATIDYL CHOLINE / phospholipidYM
Source	rattus norvegicus (Norway rat)
Keywords	TRANSPORT PROTEIN / Na+/H+ exchanger / NHE6