Publication Date
11-18-2022
Journal
iScience
DOI
10.1016/j.isci.2022.105321
PMID
36325049
PMCID
PMC9618773
PubMedCentral® Posted Date
October 2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Endocrinology, Structural biology
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.
Graphical Abstract
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Biochemical Phenomena, Metabolism, and Nutrition Commons, Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Endocrinology, Diabetes, and Metabolism Commons, Medical Cell Biology Commons