4X8Y

Crystal structure of human PGRMC1 cytochrome b5-like domain

Summary for 4X8Y

• Entry DOI: 10.2210/pdb4x8y/pdb
• Descriptor: Membrane-associated progesterone receptor component 1, PROTOPORPHYRIN IX CONTAINING FE (3 entities in total)
• Functional Keywords: receptor, membrane, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 31015.64

Authors

Nakane, T.,Yamamoto, T.,Shimamura, T.,Kobayashi, T.,Kabe, Y.,Suematsu, M. (deposition date: 2014-12-11, release date: 2016-03-23, Last modification date: 2024-11-06)

Primary citation

Kabe, Y.,Nakane, T.,Koike, I.,Yamamoto, T.,Sugiura, Y.,Harada, E.,Sugase, K.,Shimamura, T.,Ohmura, M.,Muraoka, K.,Yamamoto, A.,Uchida, T.,Iwata, S.,Yamaguchi, Y.,Krayukhina, E.,Noda, M.,Handa, H.,Ishimori, K.,Uchiyama, S.,Kobayashi, T.,Suematsu, M.
Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance
Nat Commun, 7:11030-11030, 2016

PubMed Abstract: Progesterone-receptor membrane component 1 (PGRMC1/Sigma-2 receptor) is a haem-containing protein that interacts with epidermal growth factor receptor (EGFR) and cytochromes P450 to regulate cancer proliferation and chemoresistance; its structural basis remains unknown. Here crystallographic analyses of the PGRMC1 cytosolic domain at 1.95 Å resolution reveal that it forms a stable dimer through stacking interactions of two protruding haem molecules. The haem iron is five-coordinated by Tyr113, and the open surface of the haem mediates dimerization. Carbon monoxide (CO) interferes with PGRMC1 dimerization by binding to the sixth coordination site of the haem. Haem-mediated PGRMC1 dimerization is required for interactions with EGFR and cytochromes P450, cancer proliferation and chemoresistance against anti-cancer drugs; these events are attenuated by either CO or haem deprivation in cancer cells. This study demonstrates protein dimerization via haem-haem stacking, which has not been seen in eukaryotes, and provides insights into its functional significance in cancer.

PubMed: 26988023
DOI: 10.1038/ncomms11030

Experimental method

X-RAY DIFFRACTION (1.95 Å)