Related Experiment Video

Updated: Jun 6, 2026

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
06:45

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

Published on: May 26, 2011

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

Youyun Yang1, Wei Mo, Jian-Ting Zhang

  • 1Department of Pharmacology and Toxicology and IU Simon Cancer Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States.

Biochemistry
|November 25, 2010
PubMed

Insights

Multidrug resistance (MDR) in cancer is often caused by ATP-binding cassette (ABC) transporters like ABCC1. This study identifies specific transmembrane domains (TM5 and ECL3) within ABCC1

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Multidrug resistance (MDR) is a significant challenge in cancer therapy.
  • Overexpression of ATP-binding cassette (ABC) transporters, particularly ABCC1, contributes significantly to MDR.
  • ABCC1 is believed to function as a homodimer, with a dimerization domain previously localized to the N-terminal region.

Purpose of the Study:

  • To precisely map the dimerization site of the ABCC1 transporter.
  • To investigate the specific domains and regions involved in ABCC1 homodimerization.

Main Methods:

  • Utilized co-expression and co-immunoprecipitation techniques.
  • Employed a series of deletion constructs to systematically analyze ABCC1 domains.
  • Focused on the membrane-spanning domain 0 (MSD0) and its components.

Main Results:

  • The dimerization site of ABCC1 was further refined to transmembrane helix 5 (TM5) and extracellular loop 3 (ECL3) within MSD0.
  • Interaction between TM5 and ECL3 of one ABCC1 subunit with the corresponding regions of an opposing subunit was observed.
  • Dimerization appears sequence-independent but relies on the physical location, hydrophobicity of TM5, and length of ECL3.

Conclusions:

  • TM5 and ECL3 in MSD0 are critical for ABCC1 homodimerization.
  • Understanding these interactions may offer novel strategies to overcome ABCC1-mediated MDR in cancer treatment.

More Related Videos

ABCG5/G8 Crystallization in a Lipidic Bicelle Environment for X-Ray Crystallography06:47

ABCG5/G8 Crystallization in a Lipidic Bicelle Environment for X-Ray Crystallography

Published on: August 25, 2023

CRISPR-Mediated Reorganization of Chromatin Loop Structure09:20

CRISPR-Mediated Reorganization of Chromatin Loop Structure

Published on: September 14, 2018

Related Concept Videos

Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
Multi-pass Transmembrane Proteins and β-barrels01:09

Multi-pass Transmembrane Proteins and β-barrels

In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
Membrane Asymmetry Regulating Transporters01:19

Membrane Asymmetry Regulating Transporters

Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Insertion of Multi-pass Transmembrane Proteins in the RER01:29

Insertion of Multi-pass Transmembrane Proteins in the RER

The rough ER membrane synthesizes, assembles, and embeds transmembrane proteins in diverse topologies. These proteins function as transporters or channels and can remain in the ER membrane or are sent to the Golgi complex, lysosome, and cell membrane.
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
Single-pass Transmembrane Proteins01:25

Single-pass Transmembrane Proteins

Integral membrane proteins are tightly associated with the cell membrane and play a crucial role in cell communication, signaling, adhesion, and transport of the molecules. Some integral membrane proteins are present only in the membrane monolayer. For example, the enzyme fatty acid amide hydrolase is present in the cytoplasmic side of the membrane monolayer. In contrast, another type of integral membrane protein, also known as a transmembrane protein, spans across the membrane. Transmembrane...