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Printable Handouts
Navigable Slide Index
Topics Covered
- Domain architecture of nuclear receptors
- DNA binding domain
- Ligand binding domain
- Ligand binding pocket
- Nuclear receptors with special structural characteristics
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Merk, D. (2025, May 29). Structure of nuclear receptors [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved June 1, 2025, from https://doi.org/10.69645/VIHV7473.Export Citation (RIS)
Publication History
- Published on May 29, 2025
Financial Disclosures
- Prof. Dr. Daniel Merk has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: Nuclear Receptors as Common Therapeutic Targets
Transcript
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0:00
Hello. Welcome everyone to
Chapter 3 of the
nuclear receptors
as therapeutic targets,
HSTalk series and today
we will talk about the
structure of nuclear receptors.
0:14
Here you see, in two
different representations,
the domain architecture
of nuclear receptors
on top in the actual
tertiary structure
and at the bottom, in a
schematic representation.
As you can see, the nuclear
receptor starts with
an N-terminal domain in blue
that is typically unordered
and also varies a lot in
length and structure.
It follows a DNA-binding domain
abbreviated as DBD in yellow,
which mediates the
interaction with the DNA,
followed by a hinge
region in orange,
and then the very important
ligand binding domain,
LBD, in red at the C terminus.
1:00
These four different domains
in the nuclear receptors,
each fulfill different functions
for the nuclear receptor
or ligand-activated
transcription factor activity.
The N-terminal domain contains
the so-called activation
function 1 or AF1,
which is ligand-independent
and can,
for example, respond to
posttranslational modifications
of the nuclear receptor
and thereby modulate
its activity.
The N-terminal
domain can interact
with coregulators
and it is typically
highly disordered, but
it is the main target of
posttranslational modifications
of nuclear receptors.
It is not well conserved
within the family,
and therefore, varies a lot
in length and structure,
and it also contributes to
the stability of
nuclear receptors
and may be involved in
allosteric modulation of
the receptor structure
and activity.
The DNA-binding
domain in yellow is
highly conserved within the
family and highly structured
through the two zinc
fingers that it contains.
It mediates the DNA binding
and is also involved in
dimerization of nuclear receptors
but rather as a
secondary player and has
a weak contribution
to the dimerization.
It can also be a target of
posttranslational modifications,
and it has allosteric effects on
other domains within
the nuclear receptor.
The hinge region
is not very well
conserved and
typically disordered.
It also varies in its length
and just connects the
DNA-binding domain
with the ligand binding domain.
In addition, it can
contribute to dimerization,
and very importantly,
the hinge region
typically contains
the nuclear export signal or
the nuclear localization
signal, abbreviated as NLS,
which mediates the translocation
of the nuclear receptor
into the nucleus.
In addition, it can
also be a target to
posttranslational modifications
and interact with coregulators.
Then, in red, the very
important domain for us
that we are interested
in nuclear receptors as
therapeutic targets is
the ligand binding domain
which mediates the
ligand binding.
It contains the
activation function 2,
which is ligand-dependent,
in contrast to
the ligand-independent AF1
in the N-terminal domain.
The ligand binding
domain is overall
well conserved within the
family and highly structured.
In addition to ligand binding,
it also mediates
the dimerization of
nuclear receptors
and the interaction
with coregulators
with contributions of
the DNA-binding domain
in the hinge region or
virtually all the
different domains
but the ligand domain is key.
It can also contain a
nuclear localization signal
and be a target of
posttranslational modifications.
Now let's have a look
at all these domains,
or the important
domains, in more detail.