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TitleMultidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains.
Journal, issue, pagesNat Commun, Vol. 9, Issue 1, Page 3520, Year 2018
Publish dateAug 30, 2018
AuthorsWei Huang / Yi Peng / Janna Kiselar / Xuan Zhao / Aljawharah Albaqami / Daniel Mendez / Yinghua Chen / Srinivas Chakravarthy / Sayan Gupta / Corie Ralston / Hung-Ying Kao / Mark R Chance / Sichun Yang /
PubMed AbstractHuman estrogen receptor alpha (hERα) is a hormone-responsive nuclear receptor (NR) involved in cell growth and survival that contains both a DNA-binding domain (DBD) and a ligand-binding domain (LBD) ...Human estrogen receptor alpha (hERα) is a hormone-responsive nuclear receptor (NR) involved in cell growth and survival that contains both a DNA-binding domain (DBD) and a ligand-binding domain (LBD). Functionally relevant inter-domain interactions between the DBD and LBD have been observed in several other NRs, but for hERα, the detailed structural architecture of the complex is unknown. By utilizing integrated complementary techniques of small-angle X-ray scattering, hydroxyl radical protein footprinting and computational modeling, here we report an asymmetric L-shaped "boot" structure of the multidomain hERα and identify the specific sites on each domain at the domain interface involved in DBD-LBD interactions. We demonstrate the functional role of the proposed DBD-LBD domain interface through site-specific mutagenesis altering the hERα interfacial structure and allosteric signaling. The L-shaped structure of hERα is a distinctive DBD-LBD organization of NR complexes and more importantly, reveals a signaling mechanism mediated by inter-domain crosstalk that regulates this receptor's allosteric function.
External linksNat Commun / PubMed:30166540 / PubMed Central
MethodsSAS (X-ray synchrotron)
Structure data

SASDDU8:
Multidomain architecture of the estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains
Method: SAXS/SANS

Source
  • Homo sapiens (human)

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