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  • Meeting abstract
  • Open Access

Conformation of membrane-inserted P-glycoprotein

BMC Pharmacology201010 (Suppl 1) :A27

  • Published:


  • Homology Modelling
  • Biochemical Evidence
  • Native Membrane
  • Resistance Transporter
  • Central Pore


The human genome codes for 49 members of the large ABC protein family. Most of them are membrane transporters. The first structures of exporters have been solved in recent years. Although a remarkable achievement, some uncertainty remained with respect to the physiological conformation of the transporter, which seems not to be fully compatible with all biochemical evidence. During crystallization, the transporter is extracted from its native membrane environment and solubilized by surfactants. This procedure might have influenced the transporters' conformation and lead to the structures observed in the crystals. We focus on the multidrug resistance transporter P-glycoprotein, which prevents xenotoxic compounds from entering the body and from penetrating into the brain, and confers resistance to chemotherapy.


We used homology modelling and MD simulations to identify the equilibrium conformation of the membrane inserted transporter.


An initial P-glycoprotein model was built using the Sav1866 template [1]. The model was in compliance with most experimental data; discrepancies were observed in the central pore, where biochemical evidence suggested a smaller distance between the two sides of the wing-like helical bundles of the transmembrane region. Bending the structure allowed us to create a model that showed a consistently better agreement with biochemical data [2]. MD simulations were used to probe for the equilibrium conformation in the membrane environment. Simulations were initiated from both the Sav1866-based and from the bend model. Analysis of the two trajectories revealed a tendency to converge to a common conformation, as the simulation started from the wing-like structure showed a motion that brought the two wings closer.


Our results therefore indicate that the membrane environment does have an effect on the equilibrium conformation and that this conformation differs from the one observed in the crystal structure of the bacterial homolog Sav1866.

Authors’ Affiliations

Institute of Medical Chemistry, Medical University of Vienna, 1090, Vienna, Austria
Institute of Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, 1090, Vienna, Austria


  1. Dawson RJ, Locher KP: Structure of a bacterial multidrug ABC transporter. Nature. 2006, 443: 180-185. 10.1038/nature05155.View ArticlePubMedGoogle Scholar
  2. Stockner T, de Vries SJ, Bonvin AM, Ecker GF, Chiba P: Data-driven homology modelling of P-glycoprotein in the ATP-bound state indicates flexibility of the transmembrane domains. FEBS J. 2009, 276: 964-972. 10.1111/j.1742-4658.2008.06832.x.View ArticlePubMedGoogle Scholar


© Stockner et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.