Function and structural regulation of the carbon monoxide (CO)-responsive membrane protein PGRMC1

J Clin Biochem Nutr. 2018 Jul;63(1):12-17. doi: 10.3164/jcbn.17-132. Epub 2018 Apr 11.

Abstract

Progesterone receptor membrane associated component 1 is a multifunctional heme-binding protein that plays a role in several biological processes such as tumor progression, metabolic regulation, and viability control of nerve cells. Notably, progesterone receptor membrane associated component 1 is highly expressed in various types of cancer cells, and facilitates cancer proliferation and chemoresistance. Recently, progesterone receptor membrane associated component 1 structure has been explored by X-ray crystallographic analysis. Interestingly, whereas apo- progesterone receptor membrane associated component 1 exists as a monomer, the heme-bound progesterone receptor membrane associated component 1 converts into a stable dimer by forming a unique heme-heme stacking structure, leading to activation of epidermal growth factor receptor signaling and chemoresistance in cancer cells. Furthermore, the gas mediator carbon monoxide inhibits progesterone receptor membrane associated component 1-mediated activation in cancer cells by dissociating the heme-stacking dimer of progesterone receptor membrane associated component 1. The dynamic structural regulation of progesterone receptor membrane associated component 1 will provide new insights for understanding the mechanisms underlying its various functions.

Keywords: cancer; carbon monoxide; chemoresistance; heme; metabolism; neuron.

Publication types

  • Review