Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Specific recognition of androgens by their nuclear receptor. A structure-function study.

N Poujol1, J M Wurtz, B Tahiri

  • 1INSERM U439, Pathologie Moléculaire des Récepteurs Nucléaires, 34090 Montpellier, France.

The Journal of Biological Chemistry
|April 29, 2000
PubMed
Summary

Researchers studied the human androgen receptor (hAR) using homology modeling and mutations. Key residues like Asn(705) significantly impact ligand binding and activity, suggesting new drug design strategies for androgen receptor modulators.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Virilization at puberty in adolescent girls may reveal a 46,XY disorder of sexual development.

Endocrine connections·2023
Same author

[Environmental endocrine disruptors and fertility].

Gynecologie, obstetrique, fertilite & senologie·2021
Same author

"Idiopathic" partial androgen insensitivity syndrome in 11 grandsons of women treated by diethylstilbestrol during gestation: a multi-generational impact of endocrine disruptor contamination?

Journal of endocrinological investigation·2020
Same author

Testotoxicosis without Testicular Mass: Revealed by Peripheral Precocious Puberty and Confirmed by Somatic <i>LHCGR</i> Gene Mutation.

Endocrine research·2019
Same author

SF1 and spleen development: new heterozygous mutation, literature review and consequences for NR5A1-mutated patient's management.

Clinical genetics·2016
Same author

[Intensive training and menstrual disorders in young female: Impact on bone mass].

Gynecologie, obstetrique & fertilite·2016

Area of Science:

  • Molecular Endocrinology
  • Steroid Receptor Biology
  • Structural Biology

Background:

  • Androgens and progestins are 3-ketosteroids differing in the steroid D-ring's 17beta substituent.
  • Understanding specific ligand recognition by the human androgen receptor (hAR) is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of specific residues in the hAR ligand-binding domain (LBD) in mediating ligand recognition and transactivation.
  • To develop a homology model of the hAR LBD to guide mutation studies and drug design.

Main Methods:

  • Homology modeling of the hAR LBD based on the progesterone receptor LBD crystal structure.
  • Site-directed mutagenesis of key hAR residues (His874, Thr877, Asn705).
  • Assessment of ligand binding affinity and transactivation capacity in response to agonists and antagonists.

Related Experiment Videos

Main Results:

  • His(874) substitution had minimal impact on hAR ligand binding and transactivation.
  • Mutations at Thr(877) and particularly Asn(705) significantly altered ligand recognition, transactivation efficiency, and receptor specificity.
  • The N705A mutant exhibited progesterone receptor (PR)-like agonist binding but lost the ability to repress transactivation with nonsteroidal antagonists.

Conclusions:

  • Residues Thr(877) and Asn(705) are critical for specific ligand binding and functional activity of the hAR.
  • The N705A mutation confers PR-like agonist properties and altered antagonist response, highlighting the plasticity of the receptor.
  • Structural modeling and mutant analysis provide insights for designing novel androgen receptor modulators.