The amino terminus of the human multidrug resistance transporter ABCC1 has a U-shaped folding with a gating function

Qun Chen, Youyun Yang, Lang Li, Jian-Ting Zhang

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Multidrug resistance is a serious problem in successful cancer chemotherapy. Studies using model cell lines have demonstrated that overexpression of some members of the ATP-binding cassette (ABC) transporter superfamily, such as ABCC1, causes enhanced efflux and, thus, decreased accumulation of multiple anticancer drugs, which leads to increased cell survival. Unlike most other ABC transporters, ABCC1 has an additional membrane-spanning domain (MSD0) with a putative extracellular amino terminus of 32 amino acids. However, the function of MSD0 and the role of the extracellular amino terminus are largely unknown. In this study, we examined the structural folding and the function of the amino terminus. We found that it has a U-shaped folding with the bottom of the U-structure facing cytoplasm and both ends in extracellular space. We also found that this U-shaped amino terminus probably functions as a gate to regulate the drug transport activity of human ABCC1.

Original languageEnglish
Pages (from-to)31152-31163
Number of pages12
JournalJournal of Biological Chemistry
Volume281
Issue number41
DOIs
StatePublished - Oct 13 2006

Fingerprint

ATP-Binding Cassette Transporters
Multiple Drug Resistance
Cells
Chemotherapy
Extracellular Space
Human Activities
Pharmaceutical Preparations
Cell Survival
Cytoplasm
Membranes
Amino Acids
Drug Therapy
Cell Line
Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

The amino terminus of the human multidrug resistance transporter ABCC1 has a U-shaped folding with a gating function. / Chen, Qun; Yang, Youyun; Li, Lang; Zhang, Jian-Ting.

In: Journal of Biological Chemistry, Vol. 281, No. 41, 13.10.2006, p. 31152-31163.

Research output: Contribution to journalArticle

Chen, Qun ; Yang, Youyun ; Li, Lang ; Zhang, Jian-Ting. / The amino terminus of the human multidrug resistance transporter ABCC1 has a U-shaped folding with a gating function. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 41. pp. 31152-31163.
@article{d2a2ce3a22994927a87a09c9c726aa59,
title = "The amino terminus of the human multidrug resistance transporter ABCC1 has a U-shaped folding with a gating function",
abstract = "Multidrug resistance is a serious problem in successful cancer chemotherapy. Studies using model cell lines have demonstrated that overexpression of some members of the ATP-binding cassette (ABC) transporter superfamily, such as ABCC1, causes enhanced efflux and, thus, decreased accumulation of multiple anticancer drugs, which leads to increased cell survival. Unlike most other ABC transporters, ABCC1 has an additional membrane-spanning domain (MSD0) with a putative extracellular amino terminus of 32 amino acids. However, the function of MSD0 and the role of the extracellular amino terminus are largely unknown. In this study, we examined the structural folding and the function of the amino terminus. We found that it has a U-shaped folding with the bottom of the U-structure facing cytoplasm and both ends in extracellular space. We also found that this U-shaped amino terminus probably functions as a gate to regulate the drug transport activity of human ABCC1.",
author = "Qun Chen and Youyun Yang and Lang Li and Jian-Ting Zhang",
year = "2006",
month = "10",
day = "13",
doi = "10.1074/jbc.M603529200",
language = "English",
volume = "281",
pages = "31152--31163",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "41",

}

TY - JOUR

T1 - The amino terminus of the human multidrug resistance transporter ABCC1 has a U-shaped folding with a gating function

AU - Chen, Qun

AU - Yang, Youyun

AU - Li, Lang

AU - Zhang, Jian-Ting

PY - 2006/10/13

Y1 - 2006/10/13

N2 - Multidrug resistance is a serious problem in successful cancer chemotherapy. Studies using model cell lines have demonstrated that overexpression of some members of the ATP-binding cassette (ABC) transporter superfamily, such as ABCC1, causes enhanced efflux and, thus, decreased accumulation of multiple anticancer drugs, which leads to increased cell survival. Unlike most other ABC transporters, ABCC1 has an additional membrane-spanning domain (MSD0) with a putative extracellular amino terminus of 32 amino acids. However, the function of MSD0 and the role of the extracellular amino terminus are largely unknown. In this study, we examined the structural folding and the function of the amino terminus. We found that it has a U-shaped folding with the bottom of the U-structure facing cytoplasm and both ends in extracellular space. We also found that this U-shaped amino terminus probably functions as a gate to regulate the drug transport activity of human ABCC1.

AB - Multidrug resistance is a serious problem in successful cancer chemotherapy. Studies using model cell lines have demonstrated that overexpression of some members of the ATP-binding cassette (ABC) transporter superfamily, such as ABCC1, causes enhanced efflux and, thus, decreased accumulation of multiple anticancer drugs, which leads to increased cell survival. Unlike most other ABC transporters, ABCC1 has an additional membrane-spanning domain (MSD0) with a putative extracellular amino terminus of 32 amino acids. However, the function of MSD0 and the role of the extracellular amino terminus are largely unknown. In this study, we examined the structural folding and the function of the amino terminus. We found that it has a U-shaped folding with the bottom of the U-structure facing cytoplasm and both ends in extracellular space. We also found that this U-shaped amino terminus probably functions as a gate to regulate the drug transport activity of human ABCC1.

UR - http://www.scopus.com/inward/record.url?scp=33750046916&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750046916&partnerID=8YFLogxK

U2 - 10.1074/jbc.M603529200

DO - 10.1074/jbc.M603529200

M3 - Article

C2 - 16914551

AN - SCOPUS:33750046916

VL - 281

SP - 31152

EP - 31163

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 41

ER -