P-glycoprotein: It's as simple as ABC

What is it?

P-glycoprotein is a member of the ABC transporter family of proteins. ABC transporters are one of the oldest families of proteins and are present in bacteria, fungi and mammals. They have likely evolved as a defence mechanism to protect our cells from toxic substances. These ABC transporters, such as P-glycoprotein, sit in the membrane of the cell and play a role in pumping toxic or foreign substances out of the cell. The ABC transporters have been linked to cystic fibrosis, tumour resistance to chemotherapy, and multi-drug resistance.

What does it look like?

The structure of P-glycoprotein (pdb codes: 3G5U, 3G60 and 3G61) was determined in 2009 to 3.8 angstroms. The protein is split into four domains: two transmembrane domains (yellow) that span from inside the cell to outside the cell and, two nucleotide binding domains (purple) that bind ATP to drive the pump. For an excellent movie on the pumping motion of P-glycoprotein see https://www.youtube.com/watch?v=T8dZwSPr8i8.

Image generated by Pymol (http://www.pymol.org/) (pdb code: 3G5U).

Where does the structure come from?

The structure of P-glycoprotein was published in 2009 in Science. There are many structures of other ABC transporter family members, including the recent structure of a bacterial E.coli ABC transporter (pdb code: 4PL0), that highlights the transition of ABC transporters from inward open to outward open states.

You can read more about P-glycoprotein at: http://www.rcsb.org/pdb/101/motm.do?momID=123.

Tags: protein   defence   transporter