Spatial definition of the human progesterone receptor-B transcriptional complex
Xinzhe Yu,
Ping Yi,
Anil K. Panigrahi,
Lance Edward V. Lumahan,
John P. Lydon,
David M. Lonard,
Steven J. Lutdke,
Zhao Wang,
Bert W. O’Malley
Affiliations
Xinzhe Yu
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Ping Yi
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Center for Nuclear Receptor and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA
Anil K. Panigrahi
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Lance Edward V. Lumahan
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
John P. Lydon
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
David M. Lonard
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Steven J. Lutdke
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; CryoEM/ET Core, Baylor College of Medicine, Houston, TX 77030, USA
Zhao Wang
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; CryoEM/ET Core, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Corresponding author
Bert W. O’Malley
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Corresponding author
Summary: We report the quaternary structure of core transcriptional complex for the full-length human progesterone receptor-B (PR-B) homodimer with primary coactivator steroid receptor coactivator-2 (SRC-2) and the secondary coactivator p300/CREB-binding protein (CBP). The PR-B homodimer engages one SRC-2 mainly through its activation function 1 (AF1) in N-terminus. SRC-2 is positioned between PR-B and p300 leaving space for direct interaction between PR-B and p300 through PR-B’s C-terminal AF2 and its unique AF3. Direct AF3/p300 interaction provides long-desired structural insights into the known functional differences between PR-B and the PR-A isoform lacking AF3. We reveal the contributions of each AF and demonstrate their structural basis in forming the PR-B dimer interface and PR-B/coactivator complex. Comparison of the PR-B/coactivator complex with other steroid receptor (estrogen receptor and androgen receptor) complexes also shows that each receptor has its unique mechanism for recruiting coactivators due to the highly variable N-termini among receptors.
