8vz1 | pdb_00008vz1

Crystal Structure of the ER-alpha Ligand-binding Domain (L372S, L536S) in complex with k-409

spinqualitylabelsall models 8vz1, resolution 1.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8vz1 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.82Å Ligands: A1AHS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The estrogen receptor-alpha (ER) is thought to function only as a homodimer but responds to a variety of environmental, metazoan, and therapeutic estrogens at subsaturating doses, supporting binding mixtures of ligands as well as dimers that are only partially occupied. Here, we present a series of flexible ER ligands that bind to receptor dimers with individual ligand poses favoring distinct receptor conformations-receptor conformational heterodimers-mimicking the binding of two different ligands. Molecular dynamics simulations showed that the pairs of different ligand poses changed the correlated motion across the dimer interface to generate asymmetric communication between the dimer interface, the ligands, and the surface binding sites for epigenetic regulatory proteins. By examining the binding of the same ligand in crystal structures of ER in the agonist vs. antagonist conformers, we also showed that these allosteric signals are bidirectional. The receptor conformer can drive different ligand binding modes to support agonist vs. antagonist activity profiles, a revision of ligand binding theory that has focused on unidirectional signaling from the ligand to the coregulator binding site. We also observed differences in the allosteric signals between ligand and coregulator binding sites in the monomeric vs. dimeric receptor, and when bound by two different ligands, states that are physiologically relevant. Thus, ER conformational heterodimers integrate two different ligand-regulated activity profiles, representing different modes for ligand-dependent regulation of ER activity. Asymmetric allostery in estrogen receptor-alpha homodimers drives responses to the ensemble of estrogens in the hormonal milieu.,Min CK, Nwachukwu JC, Hou Y, Russo RJ, Papa A, Min J, Peng R, Kim SH, Ziegler Y, Rangarajan ES, Izard T, Katzenellenbogen BS, Katzenellenbogen JA, Nettles KW Proc Natl Acad Sci U S A. 2024 Jun 11;121(24):e2321344121. doi: , 10.1073/pnas.2321344121. Epub 2024 Jun 3. PMID:38830107 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA