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

Conditional activation defect of a human Gsalpha mutant

T Iiri1, Z Farfel, H R Bourne

  • 1Department of Cellular and Molecular Pharmacology, S-1212, Box 0450, University of California, San Francisco, CA 94143, USA.

Proceedings of the National Academy of Sciences of the United States of America
|May 27, 1997
PubMed
Summary
This summary is machine-generated.

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

Successful glycemic control with three times a week degludec injection by medical staff for an elderly hemodialysis patient with type 2 diabetes.

Diabetology international·2019
Same author

[The relevance of medicine in Nazi Germany to current central medical issues: its major role and the Final Solution].

Yalkut moreshet·2007
Same author

Cognitive impairment is prevalent in pseudohypoparathyroidism type Ia, but not in pseudopseudohypoparathyroidism: possible cerebral imprinting of Gsalpha.

Clinical endocrinology·2007
Same author

G-proteins and GPCrs: from the beginning.

Ernst Schering Foundation symposium proceedings·2007
Same author

[Patients' families abuse the medical and nursing staff].

Harefuah·2005
Same author

WNK4 regulates airway Na+ transport: study of familial hyperkalaemia and hypertension.

European journal of clinical investigation·2005

A mutation in the Gs alpha subunit impairs G protein activation, causing hormone resistance. This defect worsens with stimulation, highlighting the need for tight GTP binding in G protein signaling.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Trimeric G proteins mediate hormonal signals by exchanging GDP for GTP on the G protein's alpha subunit (Galpha).
  • This process is crucial for cellular responses to various hormones.

Purpose of the Study:

  • To investigate a point mutation in the Gs alpha subunit that causes an inherited disorder of hormone responsiveness.
  • To elucidate the biochemical mechanism underlying the impaired G protein activation.

Main Methods:

  • Point mutation analysis of the Gs alpha subunit.
  • Biochemical assays measuring GTP/GDP binding and adenylyl cyclase activity.
  • Analysis of mutant protein behavior under various stimulation conditions (hormonal, cholera toxin, AlF4-).

Related Experiment Videos

Main Results:

  • A specific mutation (histidine for arginine) disrupts an internal salt bridge, weakening GTP gamma-phosphate binding.
  • The mutant Gs alpha subunit exhibits a paradoxical activation defect, intensified by hormonal and other stimuli.
  • While basal GTPgammaS binding is slightly reduced, adenylyl cyclase stimulation occurs; the defect is prominent upon receptor stimulation or GTP binding interference.

Conclusions:

  • Efficient G protein activation requires the Galpha subunit to tightly bind GTP.
  • The mutation highlights the critical role of intramolecular interactions in maintaining nucleotide binding affinity.
  • This study provides insights into inherited disorders of hormone responsiveness linked to G protein dysfunction.