Structure of a human multidrug transporter in an inward-facing conformation.

Journal of Structural Biology
Mark F RosenbergRobert C Ford

Abstract

Multidrug resistance protein 1 (ABCC1) is a member of the 'C' class of ATP-binding cassette transporters, which can give rise to resistance to chemotherapy via drug export from cells. It also acts as a leukotriene C4 transporter, and hence has a role in adaptive immune response. Most C-class members have an additional NH(2)-terminal transmembrane domain versus other ATP-binding cassette transporters, but little is known about the structure and role of this domain. Using electron cryomicroscopy of 2D crystals, data at 1/6per A(-1) resolution was generated for the full-length ABCC1 protein in the absence of ATP. Analysis using homologous structures from bacteria and mammals allowed the core transmembrane domains to be localised in the map. These display an inward-facing conformation and there is a noteworthy separation of the cytoplasmic nucleotide-binding domains. Examination of non-core features in the map suggests that the additional NH(2)-terminal domain has extensive contacts on one side of both core domains, and mirrors their inward-facing configuration in the absence of nucleotide.

References

May 24, 1996·The Journal of Biological Chemistry· Bakos EB Sarkadi
Jan 1, 1996·Journal of Structural Biology·R A CrowtherJ M Smith
Nov 21, 1998·The Journal of Biological Chemistry·E BakosB Sarkadi
May 1, 1999·Journal of Structural Biology·W WriggersJ A McCammon
Dec 3, 1999·Biochimica Et Biophysica Acta·D R HipfnerS P Cole
Jul 13, 2004·The Journal of Biological Chemistry·Mark F RosenbergJohn R Riordan
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Aug 18, 2004·Current Opinion in Structural Biology·Kaspar P Locher
Apr 23, 2005·Toxicology and Applied Pharmacology·Elaine M LeslieSusan P C Cole
Jan 3, 2006·FEBS Letters·Roger G Deeley, Susan P C Cole
Mar 7, 2006·Nature Reviews. Drug Discovery·Gergely SzakácsMichael M Gottesman
Mar 28, 2006·The Journal of Biological Chemistry·Alice RothnieSusan P C Cole
Jul 6, 2006·Trends in Pharmacological Sciences·Susan P C Cole, Roger G Deeley
Aug 29, 2007·Current Opinion in Structural Biology·Kaspar HollensteinKaspar P Locher
Nov 6, 2007·Biochemical and Biophysical Research Communications·Marianne K DeGorterSusan P C Cole
Nov 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Andrew WardGeoffrey Chang
Dec 7, 2007·Trends in Biochemical Sciences·Robert C Ford, Andreas Holzenburg
Oct 25, 2008·Current Opinion in Structural Biology·Michael L OldhamJue Chen
Mar 3, 2009·Molecular Cell·Dheeraj KhareJue Chen

❮ Previous
Next ❯

Citations

Aug 28, 2014·Expert Opinion on Drug Metabolism & Toxicology·Oliver Bruhn, Ingolf Cascorbi
Apr 4, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Xiao-Jie HeQing Yang
Jan 31, 2012·Biochemical Pharmacology·Yu Fukuda, John D Schuetz
Oct 5, 2011·Essays in Biochemistry·I Barry Holland
Oct 5, 2011·Essays in Biochemistry·Joseph K ZolnerciksKenneth J Linton
Oct 5, 2011·Essays in Biochemistry·Andrew J SlotSusan P C Cole
Nov 10, 2013·PloS One·Phaneendra Kumar DuddempudiMichaela Jansen
Feb 10, 2019·Biological Chemistry·Xin MengRobert C Ford
Aug 6, 2019·SLAS Discovery·David HardyAlice J Rothnie

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.