7P5C

Cryo-EM structure of human TTYH3 in Ca2+ and GDN

Summary for 7P5C

• Entry DOI: 10.2210/pdb7p5c/pdb
• EMDB information: 13198
• Descriptor: Protein tweety homolog 3, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: membrane protein, lipid metabolism, lipid transport
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 118434.10

Authors

Sukalskaia, A.,Straub, M.S.,Sawicka, M.,Deneka, D.,Dutzler, R. (deposition date: 2021-07-14, release date: 2021-08-11, Last modification date: 2024-11-13)

Primary citation

Sukalskaia, A.,Straub, M.S.,Deneka, D.,Sawicka, M.,Dutzler, R.
Cryo-EM structures of the TTYH family reveal a novel architecture for lipid interactions.
Nat Commun, 12:4893-4893, 2021

PubMed Abstract: 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.

PubMed: 34385445
DOI: 10.1038/s41467-021-25106-4

Experimental method

ELECTRON MICROSCOPY (3.2 Å)