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

Natriuretic peptide receptor A activation stabilizes a membrane-distal dimer interface.

André De Léan1, Normand McNicoll, Jean Labrecque

  • 1Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montréal, Québec H3T 1J4, Canada. delean@pharmco.umontreal.ca

The Journal of Biological Chemistry
|January 28, 2003
PubMed
Summary

Atrial natriuretic peptide receptor A (NPRA) forms a V-shaped dimer, but this study explored an A-shaped dimer. ANP binding stabilizes the receptor dimer interface, influencing its function.

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

A combined digital microfluidic test for assessing infection and immunity status for viral disease in saliva.

Lab on a chip·2025
Same author

Specificity for a CCR5 Inhibitor Is Conferred by a Single Amino Acid Residue: ROLE OF ILE198.

The Journal of biological chemistry·2015
Same author

Discovery of a series of aryl-N-(3-(alkylamino)-5-(trifluoromethyl)phenyl)benzamides as TRPA1 antagonists.

Bioorganic & medicinal chemistry letters·2014
Same author

Discovery of a 4-aryloxy-1H-pyrrolo[3,2-c]pyridine and a 1-aryloxyisoquinoline series of TRPA1 antagonists.

Bioorganic & medicinal chemistry letters·2014
Same author

RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells.

Proceedings of the National Academy of Sciences of the United States of America·2013
Same author

Novel methodology to identify TRPV1 antagonists independent of capsaicin activation.

Journal of biomolecular screening·2012

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Atrial natriuretic peptide (ANP) stabilizes natriuretic peptide receptor A (NPRA) dimers.
  • Previous crystallographic studies suggested a V-shaped NPRA dimer with a membrane-proximal interface.
  • The role of NPRA dimer conformation in ANP binding and activation remains unclear.

Purpose of the Study:

  • To investigate the possibility of an alternative A-shaped NPRA dimer involving a membrane-distal interface.
  • To determine the structural dynamics of NPRA extracellular domains in the unliganded state.
  • To elucidate the mechanism by which ANP binding stabilizes the NPRA dimer.

Main Methods:

  • Site-directed mutagenesis to introduce a cysteine residue (W74C) in the NPRA extracellular domain.

Related Experiment Videos

  • Disulfide bond formation and reduction assays to assess dimer formation and stability.
  • ANP binding and activation assays using the NPRA(W74C) mutant.
  • Chemical crosslinking with phenylenedimaleimides (PDM) to stabilize NPRA dimers.

    • Main Results:

    • The NPRA(W74C) mutant formed constitutive covalent dimers, supporting an A-shaped dimer model with a membrane-distal interface.
    • ANP binding and activation were impaired in the constitutively dimeric NPRA(W74C) mutant.
    • ANP binding was restored upon permanent disulfide bond opening, and functional dimers could be formed using PDM crosslinking.
    • These findings suggest dynamic interfacing of membrane-distal NPRA extracellular domains in the unliganded state.

    Conclusions:

    • The unliganded NPRA extracellular domains exhibit dynamic membrane-distal lobe interactions.
    • ANP binding induces a conformational change that stabilizes the NPRA dimer with a more defined interface.
    • This study provides new insights into the structural basis of NPRA activation by ANP.