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TitleCryo-EM structures of the TTYH family reveal a novel architecture for lipid interactions.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 4893, Year 2021
Publish dateAug 12, 2021
AuthorsAnastasiia Sukalskaia / Monique S Straub / Dawid Deneka / Marta Sawicka / Raimund Dutzler /
PubMed AbstractThe Tweety homologs (TTYHs) are members of a conserved family of eukaryotic membrane proteins that are abundant in the brain. The three human paralogs were assigned to function as anion channels that ...The Tweety homologs (TTYHs) are members of a conserved family of eukaryotic membrane proteins that are abundant in the brain. The three human paralogs were assigned to function as anion channels that are either activated by Ca or cell swelling. To uncover their unknown architecture and its relationship to function, we have determined the structures of human TTYH1-3 by cryo-electron microscopy. All structures display equivalent features of a dimeric membrane protein that contains five transmembrane segments and an extended extracellular domain. As none of the proteins shows attributes reminiscent of an anion channel, we revisited functional experiments and did not find any indication of ion conduction. Instead, we find density in an extended hydrophobic pocket contained in the extracellular domain that emerges from the lipid bilayer, which suggests a role of TTYH proteins in the interaction with lipid-like compounds residing in the membrane.
External linksNat Commun / PubMed:34385445 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 4.0 Å
Structure data

13194

7p54

EMDB-13194, PDB-7p54:
Cryo-EM structure of human TTYH2 in GDN
Method: EM (single particle) / Resolution: 3.3 Å

13198

7p5c

EMDB-13198, PDB-7p5c:
Cryo-EM structure of human TTYH3 in Ca2+ and GDN
Method: EM (single particle) / Resolution: 3.2 Å

13200

7p5j

EMDB-13200, PDB-7p5j:
Cryo-EM structure of human TTYH1 in GDN
Method: EM (single particle) / Resolution: 4.0 Å

13201

7p5m

EMDB-13201, PDB-7p5m:
Cryo-EM structure of human TTYH2 in lipid nanodiscs
Method: EM (single particle) / Resolution: 3.92 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
KeywordsLIPID TRANSPORT / Membrane protein / lipid metabolism

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