Skip Navigation



PEDS Advance Access published online on August 13, 2004
Protein Engineering Design and Selection, doi:10.1093/protein/gzh058
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
17/5/463    most recent
gzh058v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Livesay, D. R.
Right arrow Articles by Subramaniam, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Livesay, D. R.
Right arrow Articles by Subramaniam, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received March 26, 2004
Revised June 24, 2004
Accepted July 8, 2004

Article

Conserved sequence and structure association motifs in antibody-protein and antibody-hapten complexes

Dennis R. Livesay 1 Shankar Subramaniam 2*

1 Department of Chemistry and National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
2 Department of Bioengineering, Department of Chemistry & Biochemistry, and San Diego Supercomputing Center, University of California at San Diego, La Jolla, CA 92037, USA

* To whom correspondence should be addressed. E-mail: shankar{at}ucsd.edu.


  Abstract

In this report, we present the association requirements across a wide variety of antibody-antigen complexes. Phylogenetic analysis clearly indicates the representative nature of our structural dataset. Antigen molecules range from small molecule haptens to complete protein structures. Common association motifs identified include five conserved tyrosine residues and a single conserved arginine residue from CDR-H3. Further, specificity is refined by a diverse array of antibody-antigen electrostatic interactions that maximize complex specificity. Through analysis of calculated pKa shifts on antigen binding, we find that these interactions are conserved at 23 alignment "hot-spot" positions. Despite consistent roles in defining substrate specificity, 16 hot-spot positions are conserved less than 50% of the time. On the other hand, because of the conserved functional role of these positions, mutant screening at hot-spots is more likely to result in increased antigen specificity than elsewhere. Therefore, we believe these results should facilitate subsequent antibody design experimentation.

Keywords: Antibody-antigen complex; Antibody-hapten complex; Ig superfamily; Molecular recognition.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
M. Li, A. Gustchina, J. Alexandratos, A. Wlodawer, S. Wunschmann, C. L. Kepley, M. D. Chapman, and A. Pomes
Crystal Structure of a Dimerized Cockroach Allergen Bla g 2 Complexed with a Monoclonal Antibody
J. Biol. Chem., August 15, 2008; 283(33): 22806 - 22814.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J.-D. Ye, V. Tereshko, J. K. Frederiksen, A. Koide, F. A. Fellouse, S. S. Sidhu, S. Koide, A. A. Kossiakoff, and J. A. Piccirilli
Synthetic antibodies for specific recognition and crystallization of structured RNA
PNAS, January 8, 2008; 105(1): 82 - 87.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Onda, S. Nagata, D. J. FitzGerald, R. Beers, R. J. Fisher, J. J. Vincent, B. Lee, M. Nakamura, J. Hwang, R. J. Kreitman, et al.
Characterization of the B Cell Epitopes Associated with a Truncated Form of Pseudomonas Exotoxin (PE38) Used to Make Immunotoxins for the Treatment of Cancer Patients
J. Immunol., December 15, 2006; 177(12): 8822 - 8834.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.