{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T15:03:27Z","timestamp":1779116607335,"version":"3.51.4"},"reference-count":46,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2012,9,15]]},"abstract":"<jats:p> The proton-coupled folate transporter (PCFT) mediates intestinal folate absorption, and loss-of-function mutations in this gene result in the autosomal recessive disorder hereditary folate malabsorption. The current study, focused on a structure-functional analysis of this transporter, identified Gly-189 and Gly-192 (a GxxG motif) located in the fifth transmembrane domain as residues that could not be replaced with alanine without a loss of function. In contrast, function was preserved when Gly-56 and Gly-59 (the other conservative GXXG motif in human PCFT) were replaced with alanine. Similarly, Gly-93 and Gly-97, which constitute the only conserved GXXXG dimerization motif in human PCFT, tolerated alanine substitution. To explore the role of this region in folate binding, the residues around Gly-189 and Gly-192 were analyzed by the substituted cysteine accessibility method. Both I188C and M193C mutants were functional and were inhibited by membrane-impermeable sulfhydryl-reactive reagents; this could be prevented with PCFT substrate, but the protection was sustained at 0\u00b0C only for the I188C mutant, consistent with localization of Ile-188 in the PCFT folate binding pocket. The functional role of residues around Gly-189 and Gly-192 is consistent with a molecular structural model in which these two residues along with Ieu-188 are accessible to the PCFT aqueous translocation pathway. <\/jats:p>","DOI":"10.1152\/ajpcell.00123.2012","type":"journal-article","created":{"date-parts":[[2012,7,12]],"date-time":"2012-07-12T05:41:49Z","timestamp":1342071709000},"page":"C673-C681","source":"Crossref","is-referenced-by-count":29,"title":["Identification of a functionally critical GXXG motif and its relationship to the folate binding site of the proton-coupled folate transporter (PCFT-SLC46A1)"],"prefix":"10.1152","volume":"303","author":[{"given":"Rongbao","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, New York;"},{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Sanghoon","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, New York;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andras","family":"Fiser","sequence":"additional","affiliation":[{"name":"Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, New York; and"},{"name":"Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. 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