Analysis of functional regulation of PGMRC1

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07011
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Keio University
• Principal Investigator: Kabe Yasuaki 慶應義塾大学, 医学部(信濃町), 講師 (20397037)
• Co-Investigator(Renkei-kenkyūsha): UCHIDA Tsuyoshi 北海道大学, 理学部, 准教授 (30343742)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ヘム / がん増殖 / 構造生物科学

Outline of Final Research Achievements

Progesterone receptor membrane component 1 (PGRMC1) 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. Crystallographic analyses revealed that PGRMC1 forms a stable dimer through stacking interactions of two protruding haem molecules. The haem iron is five-coordinated by Tyr113. Haem-mediated PGRMC1 dimerization is required for interactions with EGFR and cytochromes P450, cancer proliferation and chemoresistance against anti-cancer drugs. 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.

Free Research Field

生物学