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

A structure-based database of antibody variable domain diversity.

Christopher J Bond1, Christian Wiesmann, James C Marsters

  • 1Department of Medicinal Chemistry, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. cbond_68@yahoo.com

Journal of Molecular Biology
|April 14, 2005
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

Recombinant Human Fab Antibodies Differentially Neutralize Shiga Toxin in Renal Epithelial and Endothelial Cells.

Toxins·2026
Same author

Clarifying Frizzled 2 function in development through genetically validated mouse models.

Disease models & mechanisms·2026
Same author

Dual targeting of inhibitory EGFR epitopes with synthetic antibodies in therapeutic-resistant cancers.

Protein science : a publication of the Protein Society·2026
Same author

Structural Basis of Serine Protease Inhibition by Antibodies from Biased Fab Phage-Display Libraries.

bioRxiv : the preprint server for biology·2026
Same author

Tetravalent antibodies are more potent and efficacious erythropoiesis-stimulating agents than erythropoietin in vivo.

Protein science : a publication of the Protein Society·2026
Same author

E2 variants for probing E3 ubiquitin ligase activities.

Proceedings of the National Academy of Sciences of the United States of America·2026

Natural antibody diversity is limited, but in vitro evolution of a heavy chain variable domain (V(H)H-RIG) reveals greater structural tolerance. This suggests antibody function can be significantly enhanced beyond natural immune repertoire constraints.

Area of Science:

  • Immunology
  • Structural Biology
  • Protein Engineering

Background:

  • Natural antibody diversity is constrained by genetic and functional factors.
  • Understanding these constraints is key to antibody engineering.

Purpose of the Study:

  • To investigate the limits of structural diversity in antibody variable domains.
  • To explore the potential for enhancing antibody function through in vitro evolution.

Main Methods:

  • In vitro evolution of an autonomous heavy chain variable domain (V(H)H-RIG).
  • X-ray crystallography to determine V(H)H-RIG structure.
  • Design and selection of phage-displayed libraries for structural stability.

Main Results:

Related Experiment Videos

  • Identified structurally-tolerated diversity in complementarity-determining regions and a framework region loop.
  • Observed significantly greater sequence diversity than present in natural antibody repertoires.
  • Compiled a database of over 1000 unique, structurally-tolerated antibody sequences.

    • Conclusions:

    • Structural constraints do not fully explain sequence biases in natural antibody repertoires.
    • In vitro evolution can overcome natural limitations, enabling significant antibody function enhancement.