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Structure paper

TitleThe structural basis of the pH-homeostasis mediated by the Cl/HCO exchanger, AE2.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 1812, Year 2023
Publish dateMar 31, 2023
AuthorsQing Zhang / Liyan Jian / Deqiang Yao / Bing Rao / Ying Xia / Kexin Hu / Shaobai Li / Yafeng Shen / Mi Cao / An Qin / Jie Zhao / Yu Cao /
PubMed AbstractThe cell maintains its intracellular pH in a narrow physiological range and disrupting the pH-homeostasis could cause dysfunctional metabolic states. Anion exchanger 2 (AE2) works at high cellular pH ...The cell maintains its intracellular pH in a narrow physiological range and disrupting the pH-homeostasis could cause dysfunctional metabolic states. Anion exchanger 2 (AE2) works at high cellular pH to catalyze the exchange between the intracellular HCO and extracellular Cl, thereby maintaining the pH-homeostasis. Here, we determine the cryo-EM structures of human AE2 in five major operating states and one transitional hybrid state. Among those states, the AE2 shows the inward-facing, outward-facing, and intermediate conformations, as well as the substrate-binding pockets at two sides of the cell membrane. Furthermore, critical structural features were identified showing an interlock mechanism for interactions among the cytoplasmic N-terminal domain and the transmembrane domain and the self-inhibitory effect of the C-terminal loop. The structural and cell-based functional assay collectively demonstrate the dynamic process of the anion exchange across membranes and provide the structural basis for the pH-sensitive pH-rebalancing activity of AE2.
External linksNat Commun / PubMed:37002221 / PubMed Central
MethodsEM (single particle)
Resolution2.89 - 3.32 Å
Structure data

34287

8gv8

EMDB-34287, PDB-8gv8:
The cryo-EM structure of hAE2 with DIDS
Method: EM (single particle) / Resolution: 3.08 Å

34288

8gv9

EMDB-34288, PDB-8gv9:
The cryo-EM structure of hAE2 with chloride ion
Method: EM (single particle) / Resolution: 3.06 Å

34289

8gva

EMDB-34289, PDB-8gva:
The intermediate structure of hAE2 in basic pH
Method: EM (single particle) / Resolution: 3.25 Å

34290

8gvc

EMDB-34290, PDB-8gvc:
The cryo-EM structure of hAE2 with bicarbonate
Method: EM (single particle) / Resolution: 2.89 Å

34291

8gve

EMDB-34291, PDB-8gve:
The asymmetry structure of hAE2
Method: EM (single particle) / Resolution: 3.17 Å

34292

8gvf

EMDB-34292, PDB-8gvf:
The outward-facing structure of hAE2 in basic pH
Method: EM (single particle) / Resolution: 3.09 Å

34293

8gvh

EMDB-34293, PDB-8gvh:
Human AE2 in acidic KNO3
Method: EM (single particle) / Resolution: 3.32 Å

Chemicals

ChemComp-4KU:
2,2'-ethane-1,2-diylbis{5-[(sulfanylmethyl)amino]benzenesulfonic acid}

ChemComp-CL:
Unknown entry / Chloride

ChemComp-BCT:
BICARBONATE ION / pH buffer*YM / Bicarbonate

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

Source
  • homo sapiens (human)
KeywordsTRANSPORT PROTEIN / chloride and bicarbonate transporter human-AE2 / chloride / bicarbonate

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