4x8y

Crystal structure of human PGRMC1 cytochrome b5-like domain

spinqualitylabelsall models 4x8y, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4x8y is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: HEM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PGRC1_HUMAN Receptor for progesterone. Publication Abstract from PubMed 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 A 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. Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance.,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 Nat Commun. 2016 Mar 18;7:11030. doi: 10.1038/ncomms11030. PMID:26988023 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Progesterone receptor

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