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Spatial definition of the human progesterone receptor-B transcriptional complex.


ABSTRACT: 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.

SUBMITTER: Yu X 

PROVIDER: S-EPMC9618773 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Spatial definition of the human progesterone receptor-B transcriptional complex.

Yu Xinzhe X   Yi Ping P   Panigrahi Anil K AK   Lumahan Lance Edward V LEV   Lydon John P JP   Lonard David M DM   Lutdke Steven J SJ   Wang Zhao Z   O'Malley Bert W BW  

iScience 20221010 11


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 u  ...[more]

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