Chemical basis for the affinity maturation of a camel single domain antibody.

The Journal of Biological Chemistry
E De GenstS Muyldermans

Abstract

Affinity maturation of classic antibodies supposedly proceeds through the pre-organization of the reactive germ line conformational isomer. It is less evident to foresee how this can be accomplished by camelid heavy-chain antibodies lacking light chains. Although these antibodies are subjected to somatic hypermutation, their antigen-binding fragment consists of a single domain with restricted flexibility in favor of binding energy. An antigen-binding domain derived from a dromedary heavy-chain antibody, cAb-Lys3, accumulated five amino acid substitutions in CDR1 and CDR2 upon maturation against lysozyme. Three of these residues have hydrophobic side chains, replacing serines, and participate in the hydrophobic core of the CDR1 in the mature antibody, suggesting that conformational rearrangements might occur in this loop during maturation. However, transition state analysis of the binding kinetics of mature cAb-Lys3 and germ line variants show that the maturation of this antibody relies on events late in the reaction pathway. This is reflected by a limited perturbation of k(a) and a significantly decreased k(d) upon maturation. In addition, binding reactions and the maturation event are predominantly enthalpically driven. Theref...Continue Reading

References

Dec 21, 1989·Nature·C ChothiaW R Tulip
Jun 3, 1993·Nature·C Hamers-CastermanR Hamers
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Jones, J M Thornton
Nov 1, 1995·Protein Science : a Publication of the Protein Society·C N PaceT Gray
Mar 15, 1996·Journal of Molecular Biology·I M TomlinsonG Winter
Feb 1, 1996·Immunology Today·J C Weill, C A Reynaud
Jan 1, 1996·Advances in Protein Chemistry·E A Padlan
Jan 1, 1996·Advances in Protein Chemistry·C Milstein, M S Neuberger
Jun 13, 1997·Science·G J WedemayerR C Stevens
May 29, 1998·Immunological Reviews·M S NeubergerC Milstein
Jul 3, 1998·The EMBO Journal·M LauwereysS Muyldermans
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Feb 2, 1999·Journal of Molecular Biology·L Lo ConteJ Janin
Sep 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·J J BonifaceM M Davis
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·L T ChongP A Kollman
Dec 22, 1999·Journal of Molecular Biology·P L Yang, P G Schultz
Oct 26, 2001·Journal of Molecular Biology·K DecanniereL Wyns
Jun 6, 2002·The Journal of Biological Chemistry·Erwin De GenstKarl Andersson
May 13, 2003·Nature Structural Biology·Yili LiRoy A Mariuzza
Sep 10, 2003·Journal of Molecular Biology·Christopher J BondSachdev S Sidhu
Feb 28, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ana CauerhffBradford C Braden
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Dec 14, 2011·Analytical and Bioanalytical Chemistry·Xiangqun ZengRay Mernaugh
Jan 30, 2013·Biosensors & Bioelectronics·Kobra OmidfarMaedeh Darziani Azizi
Sep 10, 2005·Nature Biotechnology·Philipp Holliger, Peter J Hudson
Aug 1, 2013·Proceedings of the National Academy of Sciences of the United States of America·Andrew B WardGeoffrey Chang
Dec 1, 2011·The Journal of Biological Chemistry·Jochen GovaertDirk Saerens
Jan 27, 2012·DNA and Cell Biology·Kobra Omidfar, Zaynab Shirvani
Feb 7, 2009·Protein Engineering, Design & Selection : PEDS·Ana MonegalArio de Marco
Apr 8, 2014·Comptes rendus biologies·Jamal S M SabirAhmed Bahieldin
Feb 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Helen DooleyMartin F Flajnik
Jul 27, 2010·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·D SmolarekA G de Brevern
Sep 1, 2009·Cancer Letters·Andrea BellJianbing Zhang
Mar 10, 2009·Molecular Immunology·Shenghua LiJianbing Zhang
Jul 20, 2007·Proteomics·Oda Stoevesandt, Michael J Taussig
Nov 26, 2008·Veterinary Immunology and Immunopathology·S MuyldermansD Saerens
Jan 30, 2007·Journal of Molecular Biology·Robyn L StanfieldIan A Wilson
Jun 20, 2006·Biophysical Journal·Petras J Kundrotas, Emil Alexov
Dec 1, 2005·Chembiochem : a European Journal of Chemical Biology·Dirk W HeinzK Ulrich Wendt
Oct 28, 2005·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Mar 5, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·John T BatesJames E Crowe
Jun 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lavanya KrishnanDinakar M Salunke
Jul 18, 2017·European Biophysics Journal : EBJ·Thi-Huong Nguyen, Andreas Greinacher
Mar 10, 2018·Frontiers in Immunology·María Elena IezziGabriela Alicia Canziani
Nov 6, 2018·Frontiers in Immunology·Mathieu DondelingerMarylène S Vandevenne
Dec 20, 2018·BMC Structural Biology·Harmeet KaurDinakar M Salunke
May 7, 2020·Proceedings of the National Academy of Sciences of the United States of America·Igor OrlovBruno P Klaholz
Mar 7, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicole L KallewaardJames E Crowe
Mar 5, 2015·The Journal of Biological Chemistry·Romain RouetDaniel Christ

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