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

Conformational basis for SH2-Tyr(P)527 binding in Src inactivation.

Marina K Ayrapetov1, Yue-Hao Wang, Xiaofeng Lin

  • 1Department of Cell and Molecular Biology, University of Rhode Island, Kingston 02881, USA.

The Journal of Biological Chemistry
|June 23, 2006
PubMed
Summary

Src protein-tyrosine kinase inactivation relies on conformational changes, not just binding affinity, for its C-terminal tail to bind the SH2 domain. This conformational mechanism explains Src regulation.

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

Cyclic-Linear Hybrid Peptides as Molecular Transporters of Chemotherapeutic Agents.

Chemical biology letters·2026
Same author

Artificial Intelligence Integration in U.S. Healthcare Professional Degree Programs: A Rapid Scoping Review.

Research square·2026
Same author

Antimicrobial Resistance in Pediatric Infections: Current Status, Challenges, and Future Directions.

Antibiotics (Basel, Switzerland)·2026
Same author

Global Cancer Etiology: Molecular Signatures, Therapeutic Disparities, and the role of Socio-economic Determinants.

Chemical biology letters·2026
Same author

Iron-Based Nanoparticles as Delivery Tools.

Pharmaceuticals (Basel, Switzerland)·2026
Same author

Aneurysm Morphology Based on Conformal Geometry.

International journal for numerical methods in biomedical engineering·2026

Area of Science:

  • Molecular Biology
  • Protein Kinase Regulation
  • Structural Biology

Background:

  • Src protein-tyrosine kinase is a key regulator of cellular processes.
  • Src inactivation involves phosphorylation of Tyr527 and binding to its SH2 domain.
  • The precise mechanism of this intramolecular interaction remains incompletely understood.

Purpose of the Study:

  • To investigate the predominant forces governing the intramolecular binding of Tyr(P)527 to the Src SH2 domain.
  • To elucidate the structural basis for the conformational contribution in Src inactivation.
  • To propose a conformation-based model for Src inactivation.

Main Methods:

  • Binding assays using phosphopeptides mimicking the C-terminal tail and optimal ligands.
  • Analysis of SH2-Tyr(P)527 binding independence from surrounding sequences and SH2 domain mutations.

Related Experiment Videos

  • Investigation of unphosphorylated C-terminal tail binding and the role of specific residues (Trp260, Leu255) and the SH3 domain.

    • Main Results:

    • Intramolecular SH2-Tyr(P)527 binding is primarily driven by conformational contribution, not high affinity.
    • Binding is largely sequence-independent and requires specific residues (Trp260, Leu255) for effective interaction.
    • Even unphosphorylated C-terminal tail binding contributes to Src suppression, highlighting weak affinity's sufficiency.

    Conclusions:

    • Src inactivation is governed by a conformation-based mechanism rather than solely high-affinity binding.
    • Specific conformational requirements, involving residues Trp260 and Leu255, are crucial for SH2-Tyr(P)527 interaction.
    • This study proposes a unifying conformation-based model for understanding diverse Src activation mechanisms.