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TitleStructural and functional insights into the lipid regulation of human anion exchanger 2.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 759, Year 2024
Publish dateJan 26, 2024
AuthorsWeiqi Zhang / Dian Ding / Yishuo Lu / Hongyi Chen / Peijun Jiang / Peng Zuo / Guangxi Wang / Juan Luo / Yue Yin / Jianyuan Luo / Yuxin Yin /
PubMed AbstractAnion exchanger 2 (AE2) is an electroneutral Na-independent Cl/HCO exchanger belongs to the SLC4 transporter family. The widely expressed AE2 participates in a variety of physiological processes, ...Anion exchanger 2 (AE2) is an electroneutral Na-independent Cl/HCO exchanger belongs to the SLC4 transporter family. The widely expressed AE2 participates in a variety of physiological processes, including transepithelial acid-base secretion and osteoclastogenesis. Both the transmembrane domains (TMDs) and the N-terminal cytoplasmic domain (NTD) are involved in regulation of AE2 activity. However, the regulatory mechanism remains unclear. Here, we report a 3.2 Å cryo-EM structure of the AE2 TMDs in complex with PIP and a 3.3 Å full-length mutant AE2 structure in the resting state without PIP. We demonstrate that PIP at the TMD dimer interface is involved in the substrate exchange process. Mutation in the PIP binding site leads to the displacement of TM7 and further stabilizes the interaction between the TMD and the NTD. Reduced substrate transport activity and conformation similar to AE2 in acidic pH indicating the central contribution of PIP to the function of AE2.
External linksNat Commun / PubMed:38272905 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.3 Å
Structure data

EMDB-36448, PDB-8jni:
Structure of AE2 in complex with PIP2
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-36449, PDB-8jnj:
Structure of R932A/K1147A/H1148A mutant AE2
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-CL:
Unknown entry

ChemComp-PT5:
[(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho / phospholipid*YM

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / AE2 / SLC4A2 / PIP2

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