General Structure of P-GlycoproteinEdit

P-gp is a protein made up of two homologus halves connected by a flexible sequence. Each half of P-gp is made up of 6 transmembrane regions that are anchored into the membrane. Each unit also contains a site for

Proposed 2D structure of P-Glycoprotein.

ATP hydrolysis which allows for the pump to function. It has been shown that the flexible linker region is necessary for the function of the protein, but not the synthesis.[1]

Trans-membrane domainEdit

The transmembrane domains of P-gp play a very important part in the protein's function as they help create the binding pocket for foreign molecules. Many of the aromatic and hydrophic residues make up this domain of P-gp. This is important since it allows molecules to flow directly from the membrane into the pocket.[2]

The hydrophobic pocket is also quite specific in shape, which allows P-gp to differentiate binding of larger hydrophobic molecules.

ATP Binding DomainEdit

What truly makes P-gp an ABC transporter is the ATP binding domain present on the cytosilic side of the protein. P-gp has two ATP binding sites. One site per half of the protein. While ATP is hydrolyzed to change the conformation only one site is active at a time. ATP is used to change the conformation outwards as well as changing it back, resulting in a net loss of 2 ATPs.[3]

More InformationEdit

  1. Yuzo: P-Glycoprotein: Introduction
  2. Yuzo: P-Glycoprotein: Biological function
  3. Yuzo: P-Glycoprotein: Biosynthesis
  4. Yuzo: P-Glycoprotein: Gene sequence
  5. Yuzo: P-Glycoprotein: Amino acid sequence and composition
  6. Yuzo: P-Glycoprotein: Domains and structural motifs
  7. Yuzo: P-Glycoprotein: Interactions with macromolecules and small molecules
  8. Yuzo: P-Glycoprotein: Molecular biodiversity and evolution
  9. Yuzo: P-Glycoprotein: Literature overview
  10. Yuzo: P-Glycoprotein: Online resources


  1. Ambudkar, S.V., Dey, S., Hrycyna, C.A., Ramachandra, M., Pastan, I., and Gottesman, M.M. (1999). Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 39, 361–398.
  2. Aller, S.G., Yu, J., Ward, A., Weng, Y., Chittaboina, S., Zhuo, R., Harrell, P.M., Trinh, Y.T., Zhang, Q., Urbatsch, I.L., et al. (2009). Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding. Science 323, 1718–1722.
  3. Hrycyna, C.A., Ramachandra, M., Germann, U.A., Cheng, P.W., Pastan, I., and Gottesman, M.M. (1999). Both ATP sites of human P-glycoprotein are essential but not symmetric. Biochemistry 38, 13887–13899.