TY - JOUR
T1 - Plasmodium falciparum chloroquine resistance transporter is a H+ -coupled polyspecific nutrient and drug exporter
AU - Juge, Narinobu
AU - Moriyama, Sawako
AU - Miyaji, Takaaki
AU - Kawakami, Mamiyo
AU - Iwai, Haruka
AU - Fukui, Tomoya
AU - Nelson, Nathan
AU - Omote, Hiroshi
AU - Moriyama, Yoshinori
PY - 2015/3/17
Y1 - 2015/3/17
N2 - Extrusion of chloroquine (CQ) from digestive vacuoles through the Plasmodium falciparum CQ resistance transporter (PfCRT) is essential to establish CQ resistance of the malaria parasite. However, the physiological relevance of PfCRT and how CQ-resistant PfCRT gains the ability to transport CQ remain unknown. We prepared proteoliposomes containing purified CQ-sensitive and CQ-resistant PfCRTs and measured their transport activities. All PfCRTs tested actively took up tetraethylammonium, verapamil, CQ, basic amino acids, polypeptides, and polyamines at the expense of an electrochemical proton gradient. CQ-resistant PfCRT exhibited decreased affinity for CQ, resulting in increased CQ uptake. Furthermore, CQ competitively inhibited amino acid transport. Thus, PfCRT is a H+-coupled polyspecific nutrient and drug exporter.
AB - Extrusion of chloroquine (CQ) from digestive vacuoles through the Plasmodium falciparum CQ resistance transporter (PfCRT) is essential to establish CQ resistance of the malaria parasite. However, the physiological relevance of PfCRT and how CQ-resistant PfCRT gains the ability to transport CQ remain unknown. We prepared proteoliposomes containing purified CQ-sensitive and CQ-resistant PfCRTs and measured their transport activities. All PfCRTs tested actively took up tetraethylammonium, verapamil, CQ, basic amino acids, polypeptides, and polyamines at the expense of an electrochemical proton gradient. CQ-resistant PfCRT exhibited decreased affinity for CQ, resulting in increased CQ uptake. Furthermore, CQ competitively inhibited amino acid transport. Thus, PfCRT is a H+-coupled polyspecific nutrient and drug exporter.
KW - Amino acid
KW - Chloroquine
KW - Malaria
KW - Pfcrt
KW - Transporter
UR - http://www.scopus.com/inward/record.url?scp=84925424459&partnerID=8YFLogxK
U2 - 10.1073/pnas.1417102112
DO - 10.1073/pnas.1417102112
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AN - SCOPUS:84925424459
SN - 0027-8424
VL - 112
SP - 3356
EP - 3361
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 11
ER -