Role of transmembrane segment 5 and extracellular loop 3 in the homodimerization of human ABCC1

Youyun Yang, Wei Mo, Jian-Ting Zhang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Resistance to multiple anticancer agents is a major obstacle in the successful treatment of cancers. Overexpression of some ATP-binding cassette (ABC) membrane transporters such as ABCC1 has been shown to be a major contributor of multidrug resistance (MDR) in both laboratory cell line models and the clinical setting. ABCC1 has been thought to function as a homodimer with a putative dimerization domain located in the first 281 amino acid residues, including MSD0 and L0 domains. In this study, we further mapped in detail the dimerization site and placed it in TM5 and ECL3 in MSD0 using co-expression and co-immunoprecipitation of a series of deletion constructs. TM5 and ECL3 in one subunit appear to interact with TM5 and ECL3 in the opposing subunit in a sequence-independent manner, but their physical location together with the hydrophobicity of TM5 and the length of ECL3 appears to be important contributors to the dimerization ability of ABCC1.

Original languageEnglish
Pages (from-to)10854-10861
Number of pages8
JournalBiochemistry
Volume49
Issue number51
DOIs
StatePublished - Dec 28 2010

Fingerprint

Dimerization
ATP-Binding Cassette Transporters
Membrane Transport Proteins
Multiple Drug Resistance
Hydrophobicity
Hydrophobic and Hydrophilic Interactions
Immunoprecipitation
Antineoplastic Agents
Adenosine Triphosphate
Cells
Amino Acids
Cell Line
Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

Role of transmembrane segment 5 and extracellular loop 3 in the homodimerization of human ABCC1. / Yang, Youyun; Mo, Wei; Zhang, Jian-Ting.

In: Biochemistry, Vol. 49, No. 51, 28.12.2010, p. 10854-10861.

Research output: Contribution to journalArticle

Yang, Youyun ; Mo, Wei ; Zhang, Jian-Ting. / Role of transmembrane segment 5 and extracellular loop 3 in the homodimerization of human ABCC1. In: Biochemistry. 2010 ; Vol. 49, No. 51. pp. 10854-10861.
@article{9a2fa1255479471598354717fa47b916,
title = "Role of transmembrane segment 5 and extracellular loop 3 in the homodimerization of human ABCC1",
abstract = "Resistance to multiple anticancer agents is a major obstacle in the successful treatment of cancers. Overexpression of some ATP-binding cassette (ABC) membrane transporters such as ABCC1 has been shown to be a major contributor of multidrug resistance (MDR) in both laboratory cell line models and the clinical setting. ABCC1 has been thought to function as a homodimer with a putative dimerization domain located in the first 281 amino acid residues, including MSD0 and L0 domains. In this study, we further mapped in detail the dimerization site and placed it in TM5 and ECL3 in MSD0 using co-expression and co-immunoprecipitation of a series of deletion constructs. TM5 and ECL3 in one subunit appear to interact with TM5 and ECL3 in the opposing subunit in a sequence-independent manner, but their physical location together with the hydrophobicity of TM5 and the length of ECL3 appears to be important contributors to the dimerization ability of ABCC1.",
author = "Youyun Yang and Wei Mo and Jian-Ting Zhang",
year = "2010",
month = "12",
day = "28",
doi = "10.1021/bi101350x",
language = "English",
volume = "49",
pages = "10854--10861",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "51",

}

TY - JOUR

T1 - Role of transmembrane segment 5 and extracellular loop 3 in the homodimerization of human ABCC1

AU - Yang, Youyun

AU - Mo, Wei

AU - Zhang, Jian-Ting

PY - 2010/12/28

Y1 - 2010/12/28

N2 - Resistance to multiple anticancer agents is a major obstacle in the successful treatment of cancers. Overexpression of some ATP-binding cassette (ABC) membrane transporters such as ABCC1 has been shown to be a major contributor of multidrug resistance (MDR) in both laboratory cell line models and the clinical setting. ABCC1 has been thought to function as a homodimer with a putative dimerization domain located in the first 281 amino acid residues, including MSD0 and L0 domains. In this study, we further mapped in detail the dimerization site and placed it in TM5 and ECL3 in MSD0 using co-expression and co-immunoprecipitation of a series of deletion constructs. TM5 and ECL3 in one subunit appear to interact with TM5 and ECL3 in the opposing subunit in a sequence-independent manner, but their physical location together with the hydrophobicity of TM5 and the length of ECL3 appears to be important contributors to the dimerization ability of ABCC1.

AB - Resistance to multiple anticancer agents is a major obstacle in the successful treatment of cancers. Overexpression of some ATP-binding cassette (ABC) membrane transporters such as ABCC1 has been shown to be a major contributor of multidrug resistance (MDR) in both laboratory cell line models and the clinical setting. ABCC1 has been thought to function as a homodimer with a putative dimerization domain located in the first 281 amino acid residues, including MSD0 and L0 domains. In this study, we further mapped in detail the dimerization site and placed it in TM5 and ECL3 in MSD0 using co-expression and co-immunoprecipitation of a series of deletion constructs. TM5 and ECL3 in one subunit appear to interact with TM5 and ECL3 in the opposing subunit in a sequence-independent manner, but their physical location together with the hydrophobicity of TM5 and the length of ECL3 appears to be important contributors to the dimerization ability of ABCC1.

UR - http://www.scopus.com/inward/record.url?scp=78650496066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650496066&partnerID=8YFLogxK

U2 - 10.1021/bi101350x

DO - 10.1021/bi101350x

M3 - Article

C2 - 21090806

AN - SCOPUS:78650496066

VL - 49

SP - 10854

EP - 10861

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 51

ER -