RECEPTORY JĄDROWE
(ang. Nuclear Receptors)
wiązanie DNA
wiązanie hormonu/liganda
dimeryzacja
AF-1 dimeryzacja
FUNKCJA:
sygnał lokalizacji jądrowej łącznik
AF-2
AD AD
DBD
LBD
N
C
REGION:
A/B C D E F
(domena wiążąca ligand,
(domena wiążąca DNA,
ang. Ligand-Binding Domain)
ang. DNA-Binding Domain)
(na podstawie: Escriva H. et al.., 2004)
LBD
LBD
PPAR-
RXR-
Zn2+
Zn2+
Zn2+
DBD
Zn2+
DBD
Heterodimer PPAR- -RXR- związany z DNA
(na podstawie: Chandra V. et al. , 2008; PDB: 3DZY)
pierwszy moduł
palca cynkowego
N
Cys
Cys
Cys
Zn2+
Cys
drugi moduł
Cys
C
palca cynkowego
Cys
Zn2+
Cys
Cys
Domena wiążąca DNA receptora RXR
(na podstawie: Holmbeck S.M. et al. , 1998; PDB: 1RXR)
Mode of action of nuclear receptors (NRs). After diffusion through the cytoplasmic
membrane, the ligand can interact with its cognate receptor where it can exert a  non-genomic effect by interacting directly, for
example, with kinases (a). The ratio between cytoplasmic and nuclear location can vary between different receptors and is
affected by the nature of a ligand. Ligand binding modulates the interaction of the receptor with a plethora of factors. In the
absence of ligand, several nuclear receptors are believed to be bound to the regulatory regions of target genes as a corepressor
or histone deacetylase (HDAC) complex (b). Histone deacetylation is responsible for the chromatin condensation that accounts
for the gene-silencing effect of apo receptors. Ligand binding releases the HDAC complex (c) and results in the recruitment of
histone acetyltransferase (HAT) and chromatin-remodelling (CRM) complexes (d). The temporal order and requirement of these
complexes can occur in a receptor-, target-gene- and cell-specific manner. In the last step (e), the polymerase II holoenzyme,
which comprises the pol II enzyme, TAF (TATA-binding protein-associated factor) and mediator complexes, is recruited and
increases the frequency of transcription initiation.
(na podstawie: Gronemeyer H.,Gustafsson J.A., Laudet V., 2004)