Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies

Proceedings of the National Academy of Sciences of the United States of America
E De GenstLode Wyns

Abstract

Clefts on protein surfaces are avoided by antigen-combining sites of conventional antibodies, in contrast to heavy-chain antibodies (HCAbs) of camelids that seem to be attracted by enzymes' substrate pockets. The explanation for this pronounced preference of HCAbs was investigated. Eight single domain antigen-binding fragments of HCAbs (VHH) with nanomolar affinities for lysozyme were isolated from three immunized dromedaries. Six of eight VHHs compete with small lysozyme inhibitors. This ratio of active site binders is also found within the VHH pool derived from polyclonal HCAbs purified from the serum of the immunized dromedary. The crystal structures of six VHHs in complex with lysozyme and their interaction surfaces were compared to those of conventional antibodies with the same antigen. The interface sizes of VHH and conventional antibodies to lysozyme are very similar as well as the number and chemical nature of the contacts. The main difference comes from the compact prolate shape of VHH that presents a large convex paratope, predominantly formed by the H3 loop and interacting, although with different structures, into the concave lysozyme substrate-binding pocket. Therefore, a single domain antigen-combining site has a c...Continue Reading

References

Dec 21, 1989·Nature·C ChothiaW R Tulip
Jan 1, 1969·Annual Review of Biochemistry·E A Barnard
May 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·L N Kam-MorganJ F Kirsch
Jul 1, 1994·Biopolymers·R NorelR Nussinov
May 20, 1994·Journal of Molecular Biology·I K McDonald, J M Thornton
Dec 20, 1993·Journal of Molecular Biology·M C Lawrence, P M Colman
Aug 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·V ChitarraR J Poljak
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
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·D R Davies, G H Cohen
Oct 11, 1996·Journal of Molecular Biology·R M MacCallumJ M Thornton
Jan 1, 1996·Advances in Protein Chemistry·E A Padlan
Dec 1, 1996·Protein Science : a Publication of the Protein Society·R A LaskowskiJ M Thornton
Feb 12, 1998·Journal of Molecular Biology·B Al-LazikaniC Chothia
Feb 19, 1998·Journal of Molecular Biology·V MoreaA M Lesk
Jul 3, 1998·The EMBO Journal·M LauwereysS Muyldermans
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Sep 15, 2001·Antimicrobial Agents and Chemotherapy·K E ConrathS Muyldermans
Oct 26, 2001·Journal of Molecular Biology·K DecanniereL Wyns
Oct 30, 2001·Advances in Immunology·V K NguyenS Muyldermans
Apr 19, 2002·The Journal of Biological Chemistry·Aline DesmyterChristian Cambillau
Dec 17, 2002·Nature Biotechnology·Stephen A JoblingMartine E Verhoeyen
May 13, 2003·Nature Structural Biology·Yili LiRoy A Mariuzza
May 14, 2003·The Journal of Biological Chemistry·Remy LorisLode Wyns
Aug 15, 2003·Nature·Mireille DumoulinChristopher M Dobson
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
Mar 3, 2004·Acta Crystallographica. Section D, Biological Crystallography·Laurent C StoroniRandy J Read
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Jan 22, 2005·The Journal of Biological Chemistry·Erwin De GenstSerge Muyldermans
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Jun 17, 2009·Medical Microbiology and Immunology·Janusz WesolowskiFriedrich Koch-Nolte
Oct 29, 2009·Transgenic Research·Yi-Hui Audrey Teh, Tony A Kavanagh
Mar 23, 2012·Animal : an International Journal of Animal Bioscience·A FerrariJ Leoni
Jun 23, 2009·Nature Structural & Molecular Biology·C Alejandro VelikovskyRoy A Mariuzza
May 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jin HuangShohei Koide
Nov 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sven JähnichenMartine J Smit
Nov 6, 2009·The Journal of Biological Chemistry·Sharad P AdekarBrian O'Nuallain
Jan 23, 2010·The Journal of Biological Chemistry·Jeeraphong ThanongsaksrikulWanpen Chaicumpa
Apr 20, 2010·The Journal of Biological Chemistry·Willie W L KohRobin A Weiss
Oct 27, 2010·The Journal of Experimental Medicine·Sandra HubertSahil Adriouch
Apr 1, 2011·The Journal of Infectious Diseases·Lorena Itatí IbañezXavier Saelens
Jun 30, 2009·International Immunology·Louise S MathesonMarianne Brüggemann
Feb 7, 2009·Protein Engineering, Design & Selection : PEDS·Ana MonegalArio de Marco
Jun 11, 2011·Microbial Cell Factories·Ario de Marco
Nov 10, 2013·PloS One·Christian LöwPär Nordlund
Jun 5, 2013·Nanomedicine·Gholamreza Hassanzadeh-GhassabehSerge Muyldermans
Aug 2, 2013·Journal of Biochemistry·Hidetoshi InoueYoshitake Maeda
Mar 1, 2014·Nature Protocols·Els PardonJan Steyaert
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lu DengRoy A Mariuzza
Nov 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Gernot HabichtMarcus Fändrich
Apr 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Akiko KoideShohei Koide
Apr 8, 2014·Comptes rendus biologies·Jamal S M SabirAhmed Bahieldin
Feb 9, 2010·Cellular and Molecular Life Sciences : CMLS·Anske Van den AbbeeleJan Gettemans
Apr 5, 2014·Trends in Biotechnology·Thomas De MeyerAnn Depicker
Apr 3, 2014·Trends in Pharmacological Sciences·Azra Mujić-DelićMartine J Smit
Mar 5, 2013·Annual Review of Biophysics·Lu DengRoy A Mariuzza
Mar 19, 2013·Annual Review of Biochemistry·Serge Muyldermans

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