9QU3

Cryo-EM structure of the human choline transporter-like protein hCTL1 in LMNG

Summary for 9QU3

• Entry DOI: 10.2210/pdb9qu3/pdb
• EMDB information: 50252
• Descriptor: Choline transporter-like protein 1 (1 entity in total)
• Functional Keywords: membrane protein, slc44
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 73893.50

Authors

Driller, J.H.,Nel, L.,Pedersen, B.P. (deposition date: 2025-04-10, release date: 2025-05-14, Last modification date: 2026-05-27)

Primary citation

Nel, L.,Driller, J.H.,Driller, R.,Frain, K.M.,Pedersen, B.P.
Structural and biochemical comparison of the FLVCR and CTL membrane protein families in eukaryotes.
Life Sci Alliance, 9:-, 2026

PubMed Abstract: The organic cation choline is essential for eukaryotic metabolism. Recently, the feline leukemia virus subgroup C receptor-related (FLVCR, SLC49) family was demonstrated as central for basal choline transport, questioning the role of the choline transporter-like (CTL, SLC44) family in this capacity. Here, we use oocytes to confirm that FLVCR1 (SLC49A1) and FLVCR2 (SLC49A2) proteins are choline transporters. CTL1 (SLC44A1) does not transport choline under the same conditions, supported by other CTL proteins, CherI and PNS1, which also display no choline transport activity. We present the atomic structures of FLVCR2, CTL1, and PNS1. The 3.4 Å cryo-EM structure of FLVCR2 has choline in the binding pocket. The 3.3 Å cryo-EM structure of CTL1 and the 2.7 Å crystal structure of PNS1 reveal an unusual protein fold, weakly related to the mitochondrial carrier family (SLC25). The unusual fold appears incompatible with transmembrane transport and implies a different and, so far, unknown function for CTL proteins. Our results support FLVCR proteins as choline transporters and suggest a nontransport role for CTL proteins.

PubMed: 42114998
DOI: 10.26508/lsa.202503583

Experimental method

ELECTRON MICROSCOPY (3.2 Å)