Fig. 1.

Fourth transmembrane domain (TMD4) within the context of the proton-coupled folate transporter (PCFT) topological structure: partial sequence alignment of PCFT among species. A: PCFT topology has been established by the substituted Cys accessibility method (SCAM) (43). TMD4 is magnified. Leu¹⁴⁶ and Ser¹⁶⁷ are at the extracellular and intracellular interfaces, respectively. These residues and the residues between them were evaluated by the SCAM. Two residues mutated in subjects with hereditary folate malabsorption, G147R and D156Y, are indicated. B: human PCFT TMD4 protein sequence was aligned with 9 different species. PRALINE sequence alignment program (http://www.ibi.vu.nl/programs/) was utilized. Numbers above the sequence are derived from human PCFT.